Category Archives: Human Longevity

CAR T-cell therapy and bispecific antibodies for T-cell redirection are 2 recent immune strategies developed in the treatment of multiple melanoma.

Multiple Myeloma is a clonal plasma cell neoplasm characterized by bone lesions, renal impairment, cytopenias, and immunodeficiency. Despite significant therapeutic advancements in the past 2 decades that have resulted in improved survival, myeloma remains an incurable disease. The immune environment in which the cancer cells thrive is known to be a key player in the evolution of monoclonal gammopathies from premalignant stages to advanced malignancy. Further, immune dysregulationmarked by T-cell exhaustion, tolerance induction by tumor microenvironment, and tumor escape from immune surveillanceis important in the pathogenesis. Therefore, various immune strategies have been developed, including immune-enhancing drugs such as immunomodulatory drugs, checkpoint inhibitors, monoclonal antibodies, and, more recently, chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies for T-cell redirection.

CAR T cells are T lymphocytes genetically modified by viral vectors or nonviral technology such as DNA transposons to express a synthetic receptor to target a specific antigen. The single chain variable fragment (ScFV) on the ectodomain of the CAR recognizes tumor-associated antigens on the surface of tumor cells, binds to them, and initiates a cascade of cytotoxic signaling, that leads to tumor lysis.

The ectodomain is linked to the intracellular domains by a hinge/transmembrane region, commonly derived from CD8 or IgG4. The intracellular portion is the signaling domain. In the first generation of CARs, this included only the CD3 signaling

domain, which lacked a proliferation profile. The second- and third-generation CARs now include 1 (second generation) or 2 (third generation) costimulatory domains that are typically 4-1BB, CD28, and/or OX-40 to promote efficient T-cell signaling and persistence. Fourth-generation CARs (TRUCKs), which further affect the tumor microenvironment to induce cytokine production after the CAR recognizes the target antigens, and fifth-generation CARs are being developed to further improve CAR efficiency and longevity.

On the other hand, bispecific antibodies use patients unengineered T cells. The off-the-shelf antibody is designed so that 1 end binds to a multiple myeloma cell and the other end binds to a killer T cell. The first bispecific antibody for multiple myeloma was developed with an ScFV that attached to the tumor antigen and another that attached to CD3 of the T cell receptor complex of the T cell with a linker. The halflife was short and continuous infusion was required. Since then, bispecific antibodies are manufactured with an Fc segment that increases the half-life so that the agent can be administered weekly or less frequently; this is the treatment of choice in ongoing clinical trials. New agents in development include trispecific antibodies that may have a costimulatory protein or target dual myeloma antigens or antibodies that engage natural killer cells.

There are several tumor antigens being investigated as suitable targets for CAR T-cell and T-cell redirected therapies, such as CD38, CD138, SLAMF7, CD19, and more. However, the most widely studied target for both CAR T-cell therapies and for bispecific antibody therapies is B-cell maturation antigen (BCMA).

BCMA is a cell surface receptor in the tumor necrosis factor receptor superfamily member 17 (TNFRSF17). It is deemed an ideal antigenic target because it is expressed specifically on normal and malignant plasma cells but not on hematopoietic stem cells, and has higher expression on myeloma cells than normal plasma cells. It plays a key role in B-cell maturation and differentiation and promotes myeloma cell growth by binding to its ligands BAFF and APRIL. Expression of BCMA increases with progression from MGUS to advanced myeloma.

Based on encouraging results from the first major global multicenter phase 1 anti- BCMA CAR T study (NCT02658929) conducted in relapsed or refractory multiple myeloma1, investigators initiated the pivotal phase 2 KarMMa trial (NCT03361748).2 The results of this trial were updated at the 18th International Myeloma Workshop (IMW) held in Vienna, Austria, in September.3

Idecabtagene vicleucel (ide-cel; Abecma), formally bb2121, is an anti-BCMA second-generation CAR construct with a 41BB costimulatory domain. Among 128 patients enrolled in the KarMMa study, 84% were triple-class refractory. At a median follow-up of 24.8 months, the overall response rate (ORR) was 73%, with complete response (CR) or stringent CR (sCR) reported in 33% of responders. Minimal residual disease (MRD) was negative in 79% of complete responders. Further, responses were attained at a median of 1 month (range, 0.5-8.8) and the median duration of response (DOR) was 10.9 months.

The median progression-free survival (PFS) was 8.6 months and median overall survival (OS) was 24.8 months. DOR and PFS were improved in the higher-dose ranges and in complete responders. Similar degrees of responses were observed in all subgroups, including Revised International Staging System for multiple myeloma III criteria, extramedullary disease, and high tumor burden. In terms of adverse effects (AEs), cytopenias were observed in 97% of patients. Grade 3/4 neutropenia was seen in 89% of patients, grade 3/4 thrombocytopenia was seen in 52%, and grade 3/4 infections in 23%. Cytokine release syndrome (CRS) was seen in 84% of patients: 78% at grade 1/2, 6% at grade 3 or higher. CRS occurred at a median onset of 2 days and median duration was 5 days. Neurotoxicity was reported in 18% of patients, 4% of whom reported the AE as grade 3 or higher. Results of the study led to FDA approval of the first, commercially approved CAR T-cell product in March.

CARTITUDE-1 was a phase 1b/2 study (NCT03548207)4 that used a different CAR T product, ciltacabtagene autolecleucel (cilta-cel). Updated findings were presented from Usmani et al5 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at IMW from Jagannath et al.6

Cilta-cel is a lentiviral vector-based anti-BCMA construct with a 41BB costimulatory domain. The BCMA-catching domain targets 2 different epitopes simultaneously, increasing the binding affinity, and is the same CAR construct as in the Chinese trial LEGEND-2 (NCT03090659).

In CARTITUDE-1, 97 patients with a median of 6 prior lines of therapy were enrolled. At baseline, 88% were triple-class refractory and 99% were refractory to their last line of therapy. At a median follow-up of 18 months, the ORR was 98% for all patients and included an sCR rate of 80%. Responses were attained at a median of 1 month and deepened over time. The median DOR was 21.8 months overall (95% CI, 21.8-not estimable) and was not reached in patients with sCR. MRD negativity was achieved in 92.0% of evaluable patients.

The 18-month PFS rate was 66% (95% CI, 54.9%-75.0%) and the 18-month OS rate was 80.9% (95% CI, 71.4%-87.6%). These results far surpass outcomes with other nonT-cell mediated novel agent therapies in triple-class refractory patients.

In terms of safety, cytopenias were universal and 92 of 97 patients experienced any-grade CRS; 95% were grade 1/2 and had a median time of onset of 7 days and duration of 4 days. All-grade neurotoxicity was reported for 21% of patients, 10% of whom had neurotoxicity of grade 3 or higher. Although most neurotoxic events occurred in the setting of CRS, 12 patients had late neurotoxicity, 6 of whom resolved, 1 had ongoing neurotoxicity, and 1 died because of neurotoxicity. There were 21 deaths on study: 2 occurred in fewer than 100 days, 10 deaths were because of disease progression, and 6 were because of treatmentrelated AEs. Late recovery (greater than 1 month) of grade 3/4 cytopenias from first onset was seen in 10% of patients with neutropenia and 26% of those with thrombocytopenia.

At the American Society of Hematology (ASH) Annual Meeting 2020, Shah et al7 presented an analysis that compared efficacy outcomes seen in the KarMMa trial with those reported from the MAMMOTH study,8 which was a retrospective observational study of conventional care regimens in patients with triple-class refractory multiple myeloma.

The MAMMOTH study, which has been used in other comparative studies, has been a benchmark for investigators to compare therapeutic maneuvers in patients with triple-class exposed relapsed or refractory multiple myeloma who have received various standard-of-care therapies. The analysis applied matching-adjusted indirect comparisons to assess the efficacy of ide-cel and conventional care and showed that, in a matched population, ide-cel treatment was associated with a significantly higher ORR, PFS, and OS than conventional care.

Cilta-cel was similarly compared with conventional treatment in the MAMMOTH study and was presented by Costa et al at ASCO 2021.9 The MAMMOTH data set was used to identify patients with multiple myeloma refractory to anti- CD38 monoclonal antibodies who would meet eligibility for CARTITUDE-1 and who received conventional therapy. The intention-to-treat population (ITT) in CARTITUDE-1 was defined as patients who underwent apheresis, and a modified ITT population was defined as subset of patients who received cilta-cel at the recommended phase 2 dose (RP2D).

ORR, PFS, and OS for both the ITT population and modified ITT population in CARTITUDE-1 vs matching MAMMOTH cohorts were found to be superior. Specifically, the ORR in the ITT cohort was higher in CARTITUDE-1 compared with the MAMMOTH counterpart (84% vs 28%). Patients in the CARTITUDE-1 ITT cohort vs MAMMOTH cohort had improved PFS and OS rates at 12 months, 73% vs 12% and 83% vs 39%, respectively. Comparing the modified ITT cohorts, patients in CARTITUDE-1 had superior ORR (96% vs 30%), 12-month PFS rate (79% vs 15%) and 12-month OS rate (88% vs 41%).

Therefore, in patients with relapsed or refractory multiple myeloma beyond therapy with immunomodulatory drugs, proteasome inhibitor, and anti-CD38 monoclonal antibody, treatment with ide-cel or cilta-cel is associated with higher response rate and superior PFS and OS when compared with conventional treatment.

Other CAR T trials were reported at ASH 2020 and are being studied in various phase 1/2 trials. Research is directed at improving the efficacy and persistence of CAR products, which vary by source of product (autologous vs allogeneic CAR T cells), choice of vector (lentiviral, retroviral, or nonviral DNA transposon technology), use of humanized ScFv to prevent immunogenicity, CD4/CD8 ratio controlled to enrich for central memory phenotype to improve longevity of CAR T cells, dual target constructs to prevent relapses because of antigen escape, CARs against non-BCMA targets to treat BCMA negative relapses, and more.

Bispecific antibodies are in earlier stages of development than CAR T. The majority of anti bodies target BCMA, although there are some targeting antigens other than BCMA that have great potential in patients who have relapsed post BCMA-targeted therapies with BCMAnegative plasma cells.

Teclistamab is an anti-BCMA/anti-CD3 bispecific antibody with intravenous and subcutaneous formulations. Results of the MajesTEC-1 study (NCT03145181) were published in Lancet.10,11 Investigators treated 157 patients with a median of 6 prior lines of therapy, of whom 82% were triple-class refractory, 90% were refractory to their last regimen, and 85% were previously transplanted were enrolled to a dose escalation/ expansion study. A total of 40 patients received the RP2D of 1500 g/kg. At RP2D, the median time to response was 1 month and median time to CR was 3 months.

At a median follow-up of 7.2 months, median DOR was not reached (7.2-not reached). The ORR was 65% in the RP2D group, 58% had a very good partial response (VGPR) or better, and 40% had a CR or better. Importantly, the majority of patients in CR were MRD negative at 10-6. Among responders, 85% were alive and progression free at follow-up. The most common AEs of any grade were CRS, all grade 1 or 2 (70%), and neutropenia (65%). Grade 3 or 4 AEs occurred in 80% of patients, with the most common being neutropenia (40%), anemia (28%), and thrombocytopenia (20%). Infections occurred in 45% of patients and were grade 3 or higher in 23%.

Talquetamab is an anti-GPRC5D/CD3 first-in-class duo antibody. Results from the phase 1 MonumenTAL-1 trial (NCT04634552) were presented by Chari et al at ASH 202012 and updated at IMW by van de Donk et al.13

GPRC is highly expressed in poor-risk myeloma, and in hair follicles. In the MonumenTAL-1 trial, 174 patients with a median of 6 prior lines of therapy were enrolled, 102 to the intravenous arm and 72 to the subcutaneous formulation arm, in dose escalation and expansion cohorts. At baseline 71% of patients were triple-class refractory and 86% were refractory to last line of therapy; 21% of patients had received prior BCMA-targeted therapies.

The ORR was 70% at the RP2D, and 50% of responders had a VGPR or better, with a median time to first confirmed response of 1 month. Responses were durable and deepened over time, with 81% of responders continuing on treatment after a median follow-up of 6.3 months. CRS was reported in 79% of patients; 4% had CRS of grade 3/4. Median time to onset of CRS was a day after subcutaneous dose, and the duration was 2 days. Neurotoxicity was reported in 7% of patients (grade 1/2) and was mostly in the context of CRS. Grade 1/2 skin-related AEs were seen in 75% of patients and nail-related AEs in 18%. Dysgeusia was reported in 57% of patients. A phase 2 expansion study (MonumenTAL-2) is recruiting. Patients will receive talquetamab at the RP2D.

Various other bispecific antibodies are in clinical trials, including Regeneron 5458, another anti-BCMA/anti-CD3 bispecific antibody with very encouraging results reported at ASH last year.14 The ORR was 63% and responses were achieved by 1 month. The median DOR was 6 months, and among responders with more than 6 months of follow-up, 83% had ongoing responses for up to 13 months and 74% of responders remained on treatment. TNB-383B is a fully human triple-chain BCMA CD3 bispecific antibody with a unique anti-CD3 moiety for target lysis with minimal cytokine release and 2 anti-BCMA moieties. It is administered intravenously every 3 weeks without step-up dosing. Data for 58 patients from the ongoing first-in-human study were presented at ASH 2020.15 Safety data were comparable with results of other studies.

Cevostamab is another nonBCMA bispecific antibody. The target antigen is FcRH5, which is found on nave and memory B cells and plasma cells. The anti-FcRH5/anti-CD3 is administered intravenously every 3 weeks, and data were presented at ASH 2020 last year as well.16 Finally, CC-93269, a bispecific antibody with 1 CD3 and 2 BCMA binding sites, shows encouraging early data as well.

Future directions for bispecific antibodies include understanding resistance mechanisms, studying them in combination with various agents, and understanding sequencing strategies.

Because myeloma is marked by clonal heterogeneity, combinations of drugs with different mechanisms of action and nonoverlapping toxicities are frequently used with success. With the arrival of this new era of powerful immunotherapeutic tools such as CAR T and T-cell redirective agents, a sound understanding of their optimal use is key to maximizing their potential.

Read more from the original source:
Therapeutic Frontiers for Relapsed/Refractory Multiple Myeloma Expand With CAR T and Bispecific Antibodies - OncLive

If you ever thought that living over a 100 years could only be possible only for future generations, you might be mistaken. Technology and AI are advancing rapidly, and with the help of blockchain, longevity achievements might be not far ahead.

The Longevity Science Foundation, based in Switzerland, launched a $1 billion fund over the span of ten years for research and projects to advance human longevity and extend lifespan to 120+ years.

The non-profit organization aims to make longevity medicine available for everyone and will focus on four main research areas: therapeutics, predictive diagnostics, personalised medicine, and artificial intelligence. The foundation plans to fund the development of medical technology, which broadly includes blockchain.

Blockchain in the Medical Industry

Healthcare data is immense and creates challenges in centralization and security. On average, a hospital produces 760 terabytes of data every year. However, 80% of the data lacks structure and is inaccessible to researchers, according to an article by Garri Zmudze from Longevity Science Foundation.

The need for security and reoccurring consent of the data usage prevents progress for medical research. With the help of blockchain and AI, patient consent can be easily obtained, data can be unlocked for analysis, and its usage can be transparent.

Without blockchain, artificial intelligence lacks the ethically sourced and protected biomedical data it needs to find new solutions. Without artificial intelligence, the vast amounts of data protected by blockchain remain secure but unusable for research,the article says.

Blockchain Technology and Longevity Research

VitaDAO is a decentralized collective that funds longevity research. The web3-based organization aspires to create a world where longevity therapeutics are collectively funded, owned and governed by the population that will benefit from them.

VitaDAOs ecosystem has an open structureeveryone who owns VITA tokens can access it. To get the tokens, you need to contribute work, funds, or other resources to VitaDAO. In addition, its collective membership, rather than a CEO or a handful of grant reviewers, will decide by vote how to deploy its funding, manage its IP, and share/publish its data.

The organization already held a token auction on a crypto platform to receive funding for longevity researchers and raised $5.1 million (400% more than expected).

How Can Blockchain Help to Advance Longevity?

According to biochemist and researcher Eleanor Sheekey, there are two main ways in which blockchain can help to advance longevity. The first is through the funding of longevity projects such as through the recently launched VitaDAO. This not only raises significant funding for research projects but also aids in the commercialisation of drugs if they are successful.

The second way is by exploiting some of the features of blockchain technology such as security and storage of data, which is most relevant to the application of personalised or precision medicine whereby patient information such as genetics, blood profile data, microbiome assessments, epigenetic methylation, and sleep data could be transacted and analysed without risk of the patient data getting into the wrong hands and being exploited.

I think it is hard to tell for now what the potential of blockchain in medical research might be, but I don't foresee a future whereby blockchain technology is not a part of medical research,Sheekey told DailyCoin during an email interview.

On The Flipside

Why You Should Care?

Funding longevity projects through blockchain technology might be one of the best ways to be part of the research process. Blockchain adds many benefits to the medical industry, but poses some technical challenges.

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$1 Billion Science Fund to Use Blockchain Projects to Extend Human Lifespan By DailyCoin - Investing.com

In the early 1990s, Tom Perls met two people who would change his life. Perls, then a gerontology fellow at Harvard Medical School, was visiting Bostons Hebrew Rehabilitation Center for Ageing and needed to see a couple of patients who just happened to be over 100. But he couldnt find them in their rooms. He eventually tracked down one patient, a 103-year-old woman. She was busy playing Chopin and Mozart on the piano. Perls other patient, a 101-year-old former tailor, was discovered in the occupational health room mending his housemates clothes.

They totally surprised me and thats when the epiphany happened, says Perls, who is now based at Boston University. These folks seemed to be ageing incredibly slowly compared to other people. He wanted to figure out their longevity secrets and vowed to find as many other centenarians as he could. The project became the New England Centenarian Study, the worlds largest study of exceptionally old people.

Centenarians are less rare than they used to be. In the UK, there were 15,120 centenarians alive in 2020 (almost double the figure in 2002), according to the Office for National Statistics. But becoming eligible for a birthday letter from the Queen is still a remarkable feat. We spoke to longevity experts about the science that might help all of us get there and the misconceptions about ageing you should stop believing.

Myth: Theres an evolutionary reason for ageing

To figure out how to slow (or even stop) ageing, we need to know why our bodies do it in the first place. But biologist Cathy Slack from Aston University, says scientists just arent sure yet. From a purely theoretical perspective, theres no beneficial reason to age, she says. We used to think ageing resulted from a buildup of reactive oxygen species (free radicals) which caused molecular damage, but recent research suggests this is unlikely to be the full story. The current most popular explanation is that ageing is an unwanted side effect of biological processes that promote growth and reproduction in our younger years, says Slack.

After a certain point, the same mechanisms that once made us fitter start making us sicker and the body fails to turn them off. Scientists call this the hyperfunction theory of ageing. Its like a tap being left on, says Slack. You need to fill the bath, but if you leave the tap on, the water overflows and you flood your bathroom.

Myth: Old age automatically means poor health

Findings from Perls study of centenarians showed the pianist and the tailor werent outliers. People who make it to 100 arent just long-living, they tend to avoid serious illness until the final chapter of their lives. His participants medical histories suggest there are three broad categories of centenarian. Around 43 percent are delayers who dont exhibit age-related diseases until they reach their eighties. Another 42 percent are survivors who live with chronic disease from their 60s and 70s but it doesnt kill them. The remaining 15 percent or so are escapers - those with no clinically demonstrable disease at 100 years and over.

Its true that age is a major risk factor for many serious illnesses such as heart disease, dementia and diabetes. But Perls believes the old adage the older you get, the sicker you get is false. He prefers to think of it as the older you get, the healthier youve been.

Myth: Theres nothing you can do to prevent death

Its likely that centenarians, and especially super-centenarians (people who live to 110 and over) have genetic variants which protect them from age-related disease, says Perls. But genetics isnt the full picture when it comes to longevity. In fact, research suggests only about 25 per cent of the variation in human lifespan is down to genes. Health-related behaviours and the environment make up the lions share.

Just look to Californias Seventh Day Adventists, says Perls. People from this Christian denomination tend to live up to a decade longer than the average Californian. They dont smoke, drink, or eat meat, which might explain it. Perls thinks most of us could make it into our nineties simply by following a reasonably healthy lifestyle from middle age.

Nutritional epidemiologist Frank Hu, from Harvard TH Chan School of Public Health, agrees. His research, published in the British Medical Journal in 2020, uncovered five lifestyle factors that could gift you ten extra years of life. People whod never smoked, didnt drink much, had a normal BMI, exercised for around 30 minutes a day, and ate a high-quality diet expanded not only their lifespan but also the number of years they lived without serious diseases, such as diabetes, heart disease and cancer. The findings are cause for optimism, says Hu. You dont need to go vegan or run a marathon. Small healthy tweaks might extend your life significantly.

Stopping senescence could be key to living long

Other longevity research zooms in on a type of cell that accumulates in our tissues as we get older. These cells no longer multiply, but they also refuse to die. Biologists once dismissed these zombies, called senescent cells, as irrelevant to health and disease. But some researchers now believe manipulating them could be key to better ageing. Biochemist Judith Campisi from the Buck Institute for Research on Aging in California found senescent cells ooze inflammatory proteins that damage tissue and halt surrounding cells from carrying out their normal processes. Removing them from the body might therefore slow down age-related decline.

In James Kirklands laboratory at Mayo Clinic, Minnesota, mice given drugs called senolytics, which selectively kill these senescent cells, survived for longer than normal and showed delayed onset of multiple conditions usually associated with ageing. Several biotech companies, such as Unity Biotechnology, have since set their sights on senolytics as a potential fountain of youth.

Continued here:
The science that could help you live to 100 - Wired.co.uk

It might sound like hyperbolic gushing, but well say it anyway the Rolling Stones are not just a rock & roll band, they are the rock & roll band. Massively-talented performers. Effortless songwriters. Mythic figures. We might all be sick of people throwing around the word iconic, but they fully embody its meaning like no others. The only thing that must be conceded about the Stones, at least as of last month, is that despite indications to the contrary thus far, they are not immortal. And that was a hard pill to swallow for an uber-fan, which, if you havent already guessed, this writer happens to be. Charlie Watts really is gone and his presence is missed in the musical sense, but also in the spiritual sense.

It was definitely felt at the Rolling Stones Sofi Stadium shows last Thursday and this past Sunday. People even toted signs commemorating the drummer and the shows began with a video montage highlighting his contributions throughout the bands nearly 60-year long career. A lot has been said about Mr. Watts being the foundation of the band, perpetually un-showy as a skinsman, and as a person. Though technicality and aggression is what gets a drummer noticed, Charlie was simply the rock steady, smooth and solid, keeping the guys in front of him on track. This has real value, one might guess never more so than back in the day when Keith Richards was a junkie and Mick Jagger was taking the egotistical frontman role a little too far for his comrades tastes. When Charlie passed away on Aug. 24, the most shared story about him was tellingly, the fight he, Mick and Keith had over the singers solo album. He reportedly said, Never call me your drummer again, youre my singer, but that story over-simplified the dynamics of the band and their brotherly relationship.

Over the years the eldest Stone represented a distinguished contrast to his music mates flash (jumpin or otherwise) and watching the group for the first time live without him on Sunday, was as bittersweet as we thought it would be. Sonically, fill-in Steve Jordan (who played with Keith and had been a pal of Charlies for 40 years) did a great job, though, providing a fierce and funky-when-needed rhythmic base for the bands set list, which we thought was quite refreshing selection-wise compared to past stadium sets. (Well note here that we have seen every L.A. stadium gig since 1989, plus their shows at The Hollywood Bowl, Desert Trip, The Henry Fonda Theatre and The Echoplex see a few links to our past reviews at the end of this one).

The opening number, Street Fighting Man, is a familiar choice and really, a perfect choice for right now, as its often called their most politically-driven song, inspired by anti-war protests. Less literally, it evokes disruption and expressive uprising. Riff-wise its catchy as hell. Though Exile on Main Street is often cited as the Stones best work, we usually get Shine A Light and Tumbling Dice (the latter, they did play Sunday). But All Down the Line captures Exiles twangy spirit and hearing it at the start of the show was a real gift, as was the 60s-era gem, 19th Nervous Breakdown, which followed.

Beast of Burden, Wild Horses (the fan voted track, but not by us we voted for Worried About You off of Tattoo You via the website, mostly because we melt for Micks falsetto) and You Cant Always Get What You Want made for a beautiful, sing-a-long worthy mid-tempo block, followed by the new number about the pandemic, Ghost Town, and two more crowd-pleasers Start Me Up (ok, some of us are sick of that one, but the more casual fans in the crowd clearly didnt agree) and Honky Tonk Woman.

Its a running joke amongst fans that the Keef portion of a Stones show is bathroom break time, but never for this one. Weve always loved his old wino screech, especially when its in harmony with Micks deeper croon. As hes gotten older, its gotten weaker, but no matter, its the moment when the personification of cool takes the spotlight and missing it feels like a crime. Still, Richards take on Connection from Between the Buttons was honestly not the best, and we wished that itd been sung by both of the glimmer twins. Before They Make Me Run off Some Girls, with its lively yet languid chorus was better; after all its about moving while its still fun, and he proved that it is indeed, for all of us.

The rest of the set was well, just take a look at it above (and the previous dates below). Perfect. Some of the biggest, best and most badass hits by any rock band ever, living or dead, from the 60s and 70s, right there. The arrangement on Miss You was a little different (or maybe Mick forgot the words) but either way it felt joyful and jammy. The rest, all from their earlier albums, were rendered as good as anyone could possibly imagine they could be, and not just for their age, either. We had incredible floor seats and the sound was great, but apparently our friends in the nosebleeds werent so lucky, as Sofi is mostly meant for sporting events. That said the $5 billion venue is quite the looker, even if a parking spot took an hour to get to upon entry and there was a bottleneck smash to get onto the floor. Under normal circumstances wed have probably welcomed bonding with our fellow tongue-teed Stone-rs, but in COVID-19 times, not so much. At least they really did check vaccinations, which we were grateful for after dealing with the hordes.

One song notably missing from the set was Brown Sugar, a source of controversy this tour, as the band made a conscious decision not to play it. Its getting a lot of press, but for fans, the questionable nature of the track is nothing new (we even wrote about it a bit here). The references to slavery meshed with overtly sexual double entendre (about Micks girlfriend at the time, Marsha Hunt) and jubilant hooks make it kind of a mess in terms of tone, but its an infectious one that probably became popular precisely because its as sleazy as it is catchy. Its the first track on the crotch-covered Sticky Fingers, after all.

As far back as the 90s, Jagger admitted that the mishmash was problematic, but lets be honest, most of us dont sing the verses at least not the whole of them even if we savor the sweet refrain of the chorus (how come you dance so good?). Whatever motivated the chaps to finally stop performing it now doesnt really matter. We respect their decision, especially as musicians whove always shown respect for Black people and their artistry as their main inspirations (Chuck Berry, James Brown, Little Richard and all the Blues greats), collaborators and friends. Backup singer Bernard Fowler is practically the 6th member and Lisa Fischer and Blondie Chaplin shared the spotlight on past tours for years. Current female back-up singer Sasha Allen got to hold her own with Mick, wowing on Gimme Shelter during the encore, and bassist Darryl Jones and now Jordan, all feel like a cohesive part of the band, each getting moments to shine on stage and the jumbo-trons, accordingly.

Speaking of the blues, the other clickbait of recent weeks involving The Stones had Paul McCartney dismissing them as nothing more than a blues band. Jagger even addressed it at the Oct. 14 show, quipping that Paul would be joining him onstage for a blues cover. In a recent interview he also pointed out an obvious truth that should quelch the cultural comparisons (but wont): The Beatles ceased being a band in 1970, while the Stones arguably enjoyed the prime of their career in the 70s and are still an actual touring band to this day, filling stadiums around the globe. Both bands are exceptional and wonderful and deserve more than the tired whos better? bouts. Both are also comprised of human beings, even if Jaggers visceral output makes him seem like hes not, the way he jumps around, dances and still sings with gusto (he even busted out the falsetto we were hoping for a couple of times on Sunday) at 78 years old.

But Charlie Watts leaving this earthly dimension was a reminder that one day the remaining Stones will indeed stop rolling. Though they dealt with death early on when Brian Jones died and had other member exits too (Mick Taylor and Bill Wyman), losing their bedrock member this year was more than huge. We dont know if this is the last tour or not, but we do know that one day, it will be. Mick will not be able to shake his hips, and despite all the memes, Keith (and Ronnie too) wont be cranking amps with the post-apocalypse cockroaches. Its a truly heartbreaking thought, especially if youve ever seen them live. And it makes what they are doing right now as they complete the No Filter tour all the more remarkable and legacy-defining.

Read some of our past reviews here:

Rolling Stones Staples Center May 3, 2013 (With Photos and Set List)

Rolling Stones The Echoplex April 27, 2013

Last Night's Rolling Stones Set Somehow Lived up to the Hype

See the original post here:
The Rolling Stones at SoFi Stadium Show Affirmed the Band's Longevity and Legacy - L.A. Weekly

At this point, were all familiar with the trope. A local news station visits a retirement home to celebrate Muriels 106th birthday. Shes deaf or blind or both or neither, sitting in a wheelchair in the good spot next to the TV set, and a reporter asks her her secret. Youve lived through both World Wars?! Howd you do it? Then Muriel gets to flash a mischievous grin and tells us she smoked a pack a day for 50 years.

Interacting with centenarians in this way has long made them seem like circus oddities. It trivializes the concept of lifespan and longevity, reducing the science to a throw-your-hands-in-the-hair Who the hell knows! It reinforces the idea that our time on this planet isnt necessarily under our control. If my dad had a stroke and his dad had a stroke then ones probably coming for me too, right? If I make it to 80, or god forbid 90, Ive just beaten the odds. Right?

Not exactly. Since the mid-1990s, in fact, following the infamous Danish twins study, researchers have understood longevity to be only moderately heritable. For a while, this spawned estimates that genetics accounted for somewhere between 20 and 30% of ones longevity. More recently, scientists have concluded that the true heritability of human longevity at birth is closer to just 7%.

Where does that other 93% come from? Your lifestyle. Your decisions. Your everyday habits, big and small. Its possible to put years on your life, to surge past both average life expectancy and your own expectations, by resolving to live a certain way. The crazy part? This doesnt involve some complex Ponce de Lenian quest. You dont even have to search far and wide for the answers.

Thanks to the efforts of vanguard sociologists, geneticists and historians, we know where the worlds largest concentration of centenarians live and how they spend their days. (Theyre called Blue Zones, and the way people cook, move and even happy hour in them is truly revelatory.) We also know, courtesy of a renowned doctor with whom we spoke last year, that certain behaviors can decelerate cellular aging and push the human lifespan into hitherto uncharted territories, and also that we should probably stop eating hot dogs.

You might wonder: Why would I want to live longer? Doesnt the end of life look drawn out, expensive and horrible? Why would I sign up for decades of suffering? Well, the latest wave of longevity research isnt focused on living years for the sake of years. Its concerned with quality years.

Think about it. More years to travel, to exercise, to spend time with your family and whatever new family comes along. An entire life of creativity and challenges to enjoy after retirement. And consider this: those who make it to 100 are no more likely to die at 108 years old than 103. Genetics do start to factor in a bit more once you get way up there in age (hence how the Muriels of the world make it to 106), but overall, your risk of dying from any of the usual diseases plateaus. Longevity wizards only really suffer in the last couple years of their lives.

Take note this movement is going to happen, with or without you. With an assist from modern medical care, scientists project there will be 25 million centenarians scattered across the world by 2100. (There are currently just 573,000.) But you dont need to wait for Benjamin Button patents from the big pharmaceuticals. You can start living in the name of longevity today.

Below, 100 ways to live to 100, broken down by how you optimize your lifespan through diet, fitness, good choices and some truly wild wild cards. Before diving in, understand that you cant do all of them; some of them are likely even incompatible. But the idea is to cherrypick those that work for your life. Ultimately, if nothing else, know this: making the call right now to act in the name of longevity whether your right now is 35 or 65 wont just add life to your ledger. Itll enrich and lighten every year along the way.

Illustration by Santiago Usano

The planets longest-living communities all have access to food from farms and orchards down the road thats to say, within a 10-mile radius of their homes. These ingredients arent treated with pesticides or pumped with preservatives; theyre their original nutrient-dense, fiber-rich selves. Sound expensive? So are late-life medical bills.

So youll eat carrots, beets and cucumbers and thats it. Okay. But if you want to unlock your true longevity potential and lower your risk of everything from cardiovascular disease to macular degeneration you need to regularly cycle through the whole menu: cruciferous veggies, dark leafy greens, edible plant stems, roots and marrows.

Hara hachi bu is a Japanese saying that translates to Eat until youre 80% full. Its an alien concept in America, where portion sizes are the biggest in the world and somehow getting larger. But finding your slightly full will directly reduce your risk of cancer, heart disease or stroke while giving your body more energy and less bloating in the short term.

As the godfather of nouvelle cuisine, Chef Fernard Point, once famously said: Butter! Give me butter! Always butter! Restaurants want customers to leave happy, so they use lots of flavor salt, sugar and fat. It all adds up. According to one study, eating out twice a day increases your chance of an early death by 95%. Cooking is your best bet.

The bread aisle is a starting point for understanding the difference between foods rich in simple carbohydrates (Wonder Bread) and those rich in complex carbohydrates (100% whole-wheat breads). The latter, for instance, rocks a ton of fiber and fuels the body in a sustainable way. Seek out more complex carbs like brown rice, oats and barley.

You dont have to give up meat. But you should know that societies full of centenarians dont eat very much of it. While meat dominates most American meals, it only appears in Blue Zone diets at a rate of five times a month, two ounces per serving. And when it does, it comes sourced from free-range animals that werent treated with hormones or antibiotics.

Keeping fish in the rotation not only takes pressure off your veggie cooking skills its also a huge life-expectancy boon. One study found that pesco-vegetarians (who eat up to three ounces of fish daily) live longest, aided by omega-3 fatty acids, vitamins and minerals. If you can, aim for non-farmed, mid-chain fish like trout, snapper and sardines.

Your last meal of the day should be your smallest, and shouldnt be eaten within three hours of heading to sleep. If youre constantly pining for a huge dinner or bedtime snack, youre probably not fueling properly throughout the day. Its stress-eating dressed up as a reward, which leads to indigestion in the near term and weight gain over time.

Dont get bogged down with YouTube videos on the right way to intermittently fast. As renowned Harvard geneticist Dr. David Sinclair told us: We dont know the best method. We do know that if yourenever hungry, if youre eating three meals a day and snacking in between, thats the worst thing you can do. It switches off your bodys defenses.

Most people have heard this one. Dark chocolate is no elixir on its own, but cacao tree seeds are part of a family of environmentally stressed plants that activate longevity pathways in other organisms when consumed. Replace your cookies and cupcakes with a little square from time to time to reap the rewards of flavanols and resveratrol.

Peanut butter and jelly sandwiches are having a moment. A few years ago, ESPN devoted a profile to the NBAs secret addiction. Tom Brady revealed not long after that the PB&J is his pregame meal of choice. And this year, a study concluded that the sandwich can add 33 minutes to your life. Remember to use whole-wheat bread and all-natural jelly.

The backbone of the centenarian diet. Beans are high in fiber, protein, iron, magnesium, potassium and B-vitamins, and low in fat and calories. They fill you up as well as meat and cook easy (serve them on their own with olive oil and a bit of sea salt, or put them in a burrito or salad). David Buettner calls beans the worlds greatest longevity food.

Sure, youve heard it forever. That doesnt make it any less true. One massive study that assessed nut consumption in approximately 119,000 Americans over 30 years found that regular nut-eaters (think a handful or two of almonds a day) reduced their risk of dying from cancer, heart disease and respiratory disease by 20%.

Olive oil giveth, butter taketh away. While butter increases bad cholesterol levels in the blood (low-density lipoproteins), olive oil is a longevity rockstar in one study, people in the highest quintile for ingesting olive oils polyphenols lived an average of 9.5 years longer after the age of 65. Just make sure youre buying extra virgin olive oil.

You dont have to ban salty and sugary treats from your life forever, but recognize that in order to avoid empty calories and reduce your risk of heart disease they cant happen every time you have a tough day at work. Thats a self-defeating choice. Save them for the right time and place, like special celebrations, when youll appreciate them the most.

For one, choking to death would really hamper your longevity goal (about one in 2,500 people die each year from choking). But slowing down while eating is also a great way to avoid overeating. Remember it takes up to 20 minutes for the stomach to process what youve eaten. Take deliberate bites. Honor the meal and the effort it took to make it.

Heres the rule: your optimal H20 per diem is one-half ounce to one ounce of water per pound of body weight. A 180-pound male, then, should aim for a little over 11 cups of water over the course of his day. Theres no need to exceed that (youll just piss it out), but reach it with regularity and your bodys command centers will repay you in kind.

Like dark chocolate, red wine comes from a plant source that is rich in cholesterol-lowering flavanols. Some are wary of linking longevity to alcohol, but learning to moderately drink red wine can also recalibrate your relationship to the drug. Having a glass (keep it under three) at the end of the day, preferably with friends, is a stress-relieving behavior.

Green tea pops up everywhere in lifespan research. One famous study found that drinking the stuff three times a week pushes back your risk of atherosclerotic cardiovascular disease and all-cause mortality. If youre a fan, take up to two cups a day. It makes sure those cardioprotective polyphenols stay in your body long-term.

A stimulant with side effects like jitters and trouble sleeping can help us live longer? Indeed. The chemical compounds in coffee aside from caffeine a wealth of antixodiants have a positive impact on mortality, especially when consumed in copious amounts. Drinking multiple cups of coffee each day can help stem chronic diseases from Type 2 diabetes to Parkinsons.

If you pick up some of the dietary habits above eat locally, sub fish, use olive oil youre already well on your way. Nutritionists are rightfully skeptical on todays litany of fad diets, but the Mediterranean diet remains well-respected for its capability to alter microbiomes, improve cognitive function, limit risk of heart disease and promote longevity.

We want food that fits our wacky preferences (separating yolks to make egg whites), has a lot of flavor (peanut butter with added sugar) or would look good on TikTok (deep-fried macaroni and cheese casseroles). But these concepts dont square away with the traditions of long-living communities, who treat and cook whole foods as theyre naturally cultivated.

Why cant 68% of the global population digest cows milk? Were not supposed to drink it. Milk and dairy, at large is too high in fat and sugar to justify its long-time anointment as the best place to turn for protein and calcium. At the very least, cows milk has no impact on longevity, so feel free to sub it for a more environmentally friendly alternative.

One month of healthy eating will confer immediate results in the realms of cell regeneration, decreased inflammation and improved digestion. Starting young is great, but it doesnt matter how old you are. Meet with your doctor beforehand to get your bloodwork done. Then come back after and note the changes, specifically in vascular health.

Your body will rebel once you ditch your unhealthy ways for a few days. It will undoubtedly feel easier to go back to butter, processed foods and the two vegetables that you actually like. But note all the positive little changes from your trips up the stairs to your trips to the bathroom. Eating healthy will change your life, then let you live more of it.

Illustration by Santiago Usano

Quality sleep is non-negotiable if you want to live a long, healthy life. Entertain a pattern of undersleeping, and exhaustion will seep into everything you do: exercise, diet, interpersonal relationships. Sleeping five hours a night doubles your risk of death. Try to log seven, and keep it right there. Too much sleep isnt great for longevity, either.

No surprises here. Yoga slows down the effects of stress on cellular aging. Multiple studies (see here and here) have sung the praises of just three months of dedicated yoga. The combination of physical effort, breathwork and meditation slows the tide of inflammation while balancing hormones (like cortisol) that cause chronic stress.

Even if you cant commit to an intensive yoga practice, finding time each day to quiet your brain is likely a life-extending habit. When we stage personal interventions to decrease brain activity, the brain increases activity of RE1-Silencing Transcription factor, a protein that allows the brain to function at a higher capacity with less strain.

Physician-dodging is a disturbing status quo for men between the ages of 35 and 54. Only 43% of that middle-aged cohort reported seeing their doctors for annual physicals.Blame it on busy-ness (or more likely, a mix of toxic masculinity and unacknowledged vulnerability), but too often men are late to diagnoses and die earlier because of it.

Functional fitness takes on an entirely new meaning by age 70, at which point most of us have a lost a quarter of the strength we had at 30 and struggle to perform basic tasks. In fact, people with low muscle strength are 50% more likely to die earlier. Start strength training early and focus particularly on grip strength, which will aid you best in old age.

Walking for just 11 minutes each day can tangibly protect the body from the mortality risks of hours spent sitting in front of a computer. Leaving the house for a walk each day like drinking tea and eating beans is something all Blue Zone communities share. Find a time of day that works for you and pencil in a daily constitutional, rain or shine.

A dose of reality on all the longevity chat: most of us arent herding goats on a bluff over the Aegean. We spend most of the day answering emails. Within that less-than-ideal situation, make sure your screen is raised to eye level, your back is set against an ergonomic chair and your feet are planted against the floor. Spinal health is critical as you age.

Or at the least, an active orgasm life, especially as you age. One Welsh study of men between the ages of 45 and 59 discovered that a high orgasmic frequency can lower mortality risk by as much as 50%. Regular sex with a partner, meanwhile, reduces stress and risk of prostate cancer, while lowering blood pressure and improving mood.

In the text neck era,a daily dead hangwill bring mobility back to your shoulders. The practice decompresses the spine and builds strength in the upper back. One minute at a time is really hard, so feel free to break the challenge into multiple increments. Oh, and dont be surprised when the move improves your grip strength, too.

Damage done to the ossicles is irreversible. Train yourself to listen to AirPods and the like on low volume. Pumping 90-decibel noise (80% of an iPhones allotted volume)into your ears for just 10 minuteswill put you on the path to tinnitus. The effect this has on quality of life is likely why people with extensive hearing loss die earlier.

When we breathe through the nose,the nasal passageway humidifies and pressurizes the air. It produces nitric oxide, a molecule that screens air particles before they make it to the lungs. Once there, the lungs have an easier, more efficient time circulating oxygen throughout the body. This isnt an easy switch (more than half of Americans breathe through their mouths), but its worth it the practice can increase lung capacity, which improves cardio-respiratory function.

Bruxism, also known as teeth grinding or jaw clenching, is a natural response in an age of constant anxiety, but it leads to terrible sleep and even tooth fractures. When youre stressing, take extra care to put space between your teeth and focus on your breathing. And while sleeping, consider a nighttime mouth guard.

Cold-temperature exposure turns white fat (the inflammatory fat linked to heart disease) into brown fat (the naturally occurring fat that produces heat) though a process called thermogenesis. Basically, your body has to burn more energy to stay warm, which jumpstarts your metabolism. Norwegian research suggests 120 minutes outside a week in winter.

According to the hydromechanics of defecation, it takes the average person only 12 seconds to do his or her business. But men often linger in the bathroom, to the point that its played for laughs in sitcoms. The habit is less than ideal: stretching across the seat inflames the veins of the anal canal and over time can lead to hemorrhoids.

When melanoma metastasizes, the five-year survival ratenose-dives from 99% down to 25%. Heres an even crazier statistic: between 1995 and 2014, 60% of those who died from head or neck melanoma were men between the ages of 15 and 39. The sun is no joke; it can snatch life away early if you arent using sunscreen and scheduling regular screenings.

Careful napping for more than an hour in the middle of the day has been linked to all-cause mortality. But a 15- to 30-minute power nap actually increases cognitive ability and alertness. It solidifies memories in the brain, relieves stress during an exhausting day and energizes afternoons for exercise or social interaction.

One of the beauties of modern exercise? It can be quick. Like, really quick. In the past decade, studies have extolled the benefits of exercising for 15 minutes, four minutes even four seconds. The rationale remains the same throughout: high-intensity, all out bursts of physical effort foster muscle growth, clean up arteries and put years on your life.

The only thing thats inherently childish about playing is that children are more likely to do it. Playing, in whatever form it may take tennis, pick-up hoops, chasing your kids with a super soaker is essential for mental health at all ages, and a crucial deviation from exercise measured solely in pain and progress.

Wait, shouldnt we make weight loss a priority? The issues a bit more nuanced. Studies indicate that overly stressing about weight loss often leads to weight cycling, defined as a process of losing weight only to regain it all over again. This strains the body. Focus on building sustainable practices instead of aiming to shed fat from your frame.

This one piggybacks on both the issue of physician-dodging and the need for sunscreen. Cancer is the second leading cause of death in the United States, with lung, colon and liver cancer accounting for the most deaths. Its imperative that you take it seriously. Start screening regularly at age 45.

Theres a reason dental hygienists get so terse when you admit to only flossing once in a while. Flossing doesnt just prevents gum disease. It can stop heart disease. When bacteria gets into the bloodstream through the mouth, arteries narrow in an immune response. This taxes vascular health. Flossing for two minutes directly influences life expectancy.

That doesnt refer to washing your sheets once a week. Sleep hygiene is an upkeep of behaviors that help you sleep. Essentially: treating the process around sleeping as sacred. Learn to keep a calm, cool, uncluttered, sleep-only bedroom and follow methods (from shutting down caffeine intake to getting blackout curtains), that shorten your sleep latency.

Running helps people live longer. That much is clear. But researchers concluded recently that the pace and distance of your run doesnt necessarily matter. Any sort of running routine (up to four-and-a-half hours total per week) will lead to a 30% reduced risk in all-cause mortality. FYI: going over that amount wont cause any harm. Just be wary of injuries.

In the battle of cardio routines, though, swimming might take the cake. The activity is perfect for aging: its low-impact, burns a ton of calories, works the whole body and encourages flexibility. No wonder that over one 32-year study, swimmers were an amazing 50% less likely to die than regular walkers and runners. Time to fish out the goggles.

Listen: chasing a six-pack is a waste of time that has no bearing on how long youll live on this planet. Overworking show muscles too often comes at the expense of a functional, full-body routine.Double down on a diverse workout scheme and a diet without non-processed ingredients and youll naturally arrive at a tighter core, anyway.

Recruiting a family member or friend for advice on your fitness journey or hiring a personal trainer or scheduling a consultation with an exercise physiologist is not a sign of weakness. Its the ultimate sign that youre ready for change, committed to turning your life around and determined to get more life out of it in the process.

Illustration by Santiago Usano

Motorcycles look great, but their mortality numbers dont. According to the NHTSA, motorcyclists are 35 times more likely to have a fatal accident than car drivers. Even survival comes with a cost: 96% of motorcycle accidents result in injury.

One of the bleakest databases youll ever see? The BASE fatality list. BASE jumping carries a risk up to eight times greater than skydiving. Its even more dangerous cousin, meanwhile wingsuit flying has a rate of one death per 500 jumps. Unsurprisingly, virtually everyone involved with the sport has a friend who died young.

Foodstuffs with added sugar, sodium and fat are killing us all. Processed food isnt supposed to be easy to give up (it comprises over half the dietary energy consumed in the United States and United Kingdom). But its critical that you cut back. Frozen pizzas, mayonnaise, Oreos and the like drastically increase your risk of cardiovascular disease.

Aside from the obvious in-moment risk of overdose (deaths from opioids and psychostimulants have been going up since 1990), chronic and high-dose drug use decelerate dopaminergic function. In simpler terms: most of the things you rely on for healthy living motor control, motivation, arousal, etc. become seriously compromised over time.

Not to sound like an elementary school health teacher, but it really is this simple. Right behind diet, tobacco use is the leading cause of premature, preventable death in the United States. And while we normally associate cigarettes with lung cancer, nicotine use can also cause cancer in the throat, esophagus, stomach, pancreas, kidney, bladder and cervix.

The majority of e-cigarettes have nicotine in them, but all of them have chemicals that will irritate your lungs. Consider: they contain propylene glycol and vegetable glycerin (which are toxic to cells), acetaldehyde, formaldehyde (which can cause lung or heart disease) and acrolein (a herbicide thats usually used to kill weeds).

The CDC: A a pattern of drinking that brings a persons blood alcohol concentration (BAC) to 0.08 g/dl or above. Think seven drinks or so per binge, with several binges a month. Health experts unilaterally agree that this is a bad idea. One study even determined that drinking 25 drinks per week at age 40 can shorten life expectancy by up to five years.

Twitter had a lot of fun with this one, but its actually true according to a recent University of Michigan study, eating a hot dog takes 36 minutes off your life. That doesnt exactly compare to a single hit of heroin (24 hours off your life!), but it could put you in a bad cycle of salty, highly processed meat. Avoid them, or save solely for the odd ballgame.

While STIs are most definitely not more fatal than traveling in a car (as one group of volunteers misestimated in a study), they can cause infertility, urinary tract problems and half a dozen different cancers. Not to mention: unprotected sex can bring overwhelming mental stress to an activity that otherwise helps us stay healthy and happy.

Every hour, someone dies from a drunk-driving incident in America. Thats over 30% of annual road deaths in the country. Even if youre a responsible driver, remember to prepare for those who arent (always wear a seat belt!) and assess other ways you engage in distracted driving. Sending one text takes your eyes off the road for five seconds.

Living close to nature decreases your risk of depression and obesity, indirectly adding years to your life. But theres such a thing as too much solitude. Rural living can also mean a repressed social life, too much time in the car, relying on Walmart for food, fending for yourself during natural disasters and traveling over an hour for emergency medical care.

Were so accustomed to taking corner-store drugs like Tylenol and Advil that we can forget theyre, well, drugs. Always follow capsule instructions to a tee. The former contains Acetaminophen (which can cause liver issues in high doses), while the latter is a nonsteroidal anti-inflammatory (which can cause gastrointestinal bleeding when taken improperly).

Calorie restriction can play a small part in adding years to your life, but unchecked calorie intake plays a very loud role in taking them away. The average American eats 3,600 calories a day (up nearly 25% from the 1960s), and the national obesity rate sits at 42.4%. Obesity coincides with common comorbidities like Type 2 diabetes, hypertension and cancer.

The scientific research on this is pretty clear, as much as it may shock the biggest guy at your gym. A reduced protein intake plays a critical role in longevity and metabolic health. Most American men currently average twice the amount of protein they actually need in a day. That comes with too much IGF-1, a growth factor that accelerates aging.

A study published in 2015 found that sticking with a tough job with an unreasonable boss, little social support or looming layoffs can literally take two years off your life. A paycheck is a paycheck, but when a job starts exerting massive mental stress over you, the body cant tell if the initial trigger is mental or physical. Itll fall apart either way.

Happy people live longer. Improve your happiness by practicing epistemic humility, an intellectual virtue predicated on the idea that one can ever know something for sure. Its meant to help us admit our imperfections and forgive others. Sounds too good to be true in the 2020s? All the more reason to give it a try.

When just 25% of your genetics are accountable for your personal longevity, it doesnt make much sense to deterministically pin your fate (or blame your behaviors) on what happened to your parents or grandparents. Learn your familial risks, yes, but approach your daily actions and decisions with confidence and hope.

Online publications really ran with the sitting is the new smoking tagline. Not quite, but sitting should be taken seriously as a public health issue. American adults sit seven hours a day, which disrupts the bodys ability to break down body fat, slows metabolism and elevates blood pressure. Get moving, even if its just for 10 minutes.

New phrase for you? Doomscrolling is excessively scrolling through news or social media feeds looking for negative updates. Its at the intersection of smartphone addictions, a terrible news cycle and our primordial need to anticipate danger. But this sort of behavior wreaks havoc on your mental health and (unsurprisingly) never solves anything.

A full eight years ago, 61% of Netflix users admitted to binge-watching content on the platform. Weve added five major streaming services since then; each has a revolving door of content and most employ hyped full-season releases. While cranking through episodes feels like a reward, it causes eye strain, backaches, weight gain and sleep deprivation.

American adults spend up to six hours on their phones each day. Some of those hours are spent doomscrolling, others pushing back sleep (66% of adults bring their phones to bed), and far too much of it involves poring over the airbrushed life updates of others. Little wonder Instagram has been likened to addictive painkillers by reputable researchers.

The Should you let your kids play football? became a culture war topic in the early 2010s on the heels of unprecedented CTE research. Honest answer: probably not. At least, avoid the full-contact version of the game, which has the highest concussion rate outside of rugby and can cause irreversible damage to the brain.

Or state parks. Or the woods behind your house. Or any public lands where you can hike, swim and camp without a professional ranger on hand to help at a moments notice. People die constantly from drowning, falls, exposure, animal encounters selfie sticks. The issue is more relevant than ever, as novice hikers flock to nature in the pandemic era.

There are 120.5 guns for every 100 people in America. An insane 73% of homicides involve a gun.The disturbing truth is you can easily find yourself in the wrong place at the wrong time in this country. Still, the least you can do is keep guns out of your home: 27,000 people go to the hospital for accidental firearm injuries each year.

Dirty air kills more people than all transportation accidents and shootings combined, accounting for the premature deaths of one in every 25 Americans. Train yourself to check the Air Quality Index (AQI) in the weather app on your iPhone. Anything over 100 means the air is considered unhealthy for sensitive groups. Your run can wait until tomorrow.

Illustration by Santiago Usano

We knew we hated shampoo. Chemicals called phthalates are found in shampoos, fragrances, cleansers and plastics. When they get into the body, they reduce the bodys stress hormone cortisol, meddle with metabolism, negatively affect the reproductive system, and can lead to extremely preventable premature deaths.

The Okinawans say ikigai, the Nicoyans in Costa Rica say plan de vida. Each phrase translates to why I wake up in the morning. Finding that why can feel random and frustrating, but it often brings people to pursuits and causes outside of themselves. And science backs this up once you believe your life matters, you get to live more of it.

Negative thought loops trick us into thinking were being productive (we psychoanalyze uncomfortable memories, prepare for imaginary dangers, relitigate life decisions), but in reality were just willingly drowning ourselves in a puddle of anxiety, activating a hormone-fueled fight or flight response that cant be addressed in the given moment.

Not necessarily a financial plan, though thats also a good idea. One surprising study displayed that working longer can help people live longer. Remember, jobs can be real-world lifelines for many they offer social engagement, days out of the house, challenging projects. Its important to have goals and communities for filling your time after retiring, too.

In Japan, shinrin-yoku refers to forest bathing, or the act of taking in nature using all of your senses. Recent studies show adults spend 93% of their time indoors, which takes a toll on mental health (stir crazy is scientific). But the exact opposite is true for spending time outdoors. A single forest bath decreases scores for depression, fatigue, anxiety.

Take a look at a map of the worlds Blue Zones. Each is concentrated along a coastline. Settling down by the sea in a so-called blue space has been linked to a 17% reduction in mortality rate. One study suggested that living within 250 meters of a seaside environment helps reduce stress levels, with the smell and sounds offering a wonderful tonic.

People who regularly play non-digital games are more likely to score well on memory and thinking tests in their 70s, a study determined in 2019. Games like cards, chess and crosswords arent just stress-relievers; they aid in cognitive function and slow down cognitive decline. Fortunately, that holds true if you come to them later in life, too.

Team sports are a longevity motherlode. They combine consistent social interaction, vigorous exercise and play, all of which convey dynamite benefits for your physical and mental health. One study even discovered that making an adult soccer league your primary mode of exercise (over solo activities like jogging) could add five years to your life.

Another reason not to get into politics lying takes years off your life. The emotional stress that comes from telling mistruths often manifests as physical stress. Whatever the momentary reward, lying increases your risk of anxiety and depression, can sabotage relationships over time and shatters your self-esteem.

Take the fortnight frequency with a grain of salt (it comes from a study commissioned by British entertainment operator O2), but we do know that live concerts are mindful, socially rich experiences. Assuming you dont need to binge drink or trip on acid every time you attend one, plugging concerts into the calendar each month is a great idea.

Make like Ian Flemings James Bond and finish your showers with an ice-cold Scottish rinse. Up to a minute (after a morning workout) is best, if you can handle it. The ritual will lower blood pressure, stimulate your immune system and can even hack your mood, releasing happy neurotransmitters like dopamine, adrenaline, norepinephrine and serotonin.

See the rest here:
100 Ways to Live to 100: A Definitive Guide to Longevity Fitness - InsideHook

Matt Fuchs

THE WASHINGTON POST Death comes for us all.

But recent research points to interventions in diet, exercise and mental outlook that could slow down ageing and age-related diseases without risky biohacks such as unproven gene therapies.

A multidisciplinary approach involving these evidence-based strategies could get it all right, said Valter Longo, a biochemist who runs the Longevity Institute at the University of Southern Californias Leonard Davis School of Gerontology.

Theres a debate, however, about how much we can increase our longevity. All humans share 99.9 per cent of their genes.

This explains why even super-agers, born with tiny genetic differences that promote longevity, almost never surpass 110. (Jeanne Louise Calment of France was an outlier, living until the age of 122, the current record). Some animals make it well beyond that mark, according to Jan Vijg, a molecular geneticist at the Albert Einstein College of Medicine. Scientists know just one way for humans to live 170 years like a giant tortoise: Become a giant tortoise.

Some experts do find it likely that someone will set a record for our species by the end of this century. Statisticians have observed a mortality plateau for very old people; although the chance of dying in a given year goes up with age, the odds seem to stop increasing after 105. Beyond this plateau, its basically a coin toss every year: Heads youll see your next birthday, tails you wont.

Becoming a full-fledged vegetarian probably isnt necessary, but, to maximise what longevity experts call healthspan, at least 50 per cent of protein should come from vegetable sources Exercise can dupe your genes into extending your span of health

But the mortality plateau is often debated. Even if its true that the risk of death levels off, this wont necessarily result in super-agers living longer than before.

Susan Alberts, a Duke University primatologist, published a paper that compared the human rate of ageing with other primates. The maximum human life expectancy has increased by about three months per year since the mid-1800s, but that can be explained by fewer early and midlife deaths.

Alberts found that the rate of decline during old age has stayed the same, mirroring other species. She believes that maximum human life span could be extended by continuing to avert early and midlife deaths, which simply increases the pool of people who could live a really long time.

Time will tell whos right regarding the life span of our species. Whats clear is that certain lifestyles help individuals live longer than they otherwise would including the genetically blessed. Harvard researchers found that healthy habits add nearly 15 years of life expectancy. Thats over USD100 trillion in healthcare savings, said Harvard biologist David Sinclair.

Not enough Americans can access healthy lifestyles, however, and were getting sick and dying earlier across economic levels compared with other countries.

People under 65 in the richest areas of the United States (US) have higher mortality than those in the poorest areas of Europe, according to a study published in September. Were going to pay if we dont do something about this rising tide of disabled people, said Judith Campisi, a biochemist at the Buck Institute for Research on Ageing.

Findings from longevity research could support better health in old age, with fewer age-related diseases and disabilities. And interestingly, many scientists believe that a certain amount and type of stress can help, thanks to evolution.

As Sinclair wrote in his 2019 book, Lifespan: Our genes didnt evolve for a life of pampered comfort. A little stress to induce hormesis once in a while likely goes a long way.

Hormesis is a process in which various stressors such as those related to diet and exercise seem to activate genes that slow down cell growth and ageing.

USING FOOD TO TRICK YOURSELF

Stress thats good for longevity can be caused by nutrition. Ideally, our ancestors enjoyed protein-rich red meat for peak energy and performance. But when hunting expeditions failed, people resorted to eating hardy plants.

Today, our bodies still infer a state of scarcity if we consume lots of vegetables, switching on the longevity genes.

Indeed, such a diet is associated with longer lives, according to the Harvard study. Becoming a full-fledged vegetarian probably isnt necessary, but, to maximise what longevity experts call healthspan, at least 50 per cent of protein should come from vegetable sources, Longo said.

He advises getting other proteins mostly from fatty fish while moderating your intake of starchy carbohydrates, such as pasta and potatoes. Research has shown that older people who routinely devour such carbs may be more likely to become cognitively impaired.

Try to replace them sometimes with foods such as lentils or extra vegetables, which have more fibre and minerals than refined carbs, said Kris Verburgh, a nutrigerontologist and author of The Longevity Code.

Another signal of scarcity that seems to switch on longevity genes is the restriction of all foods, which has been shown by decades of animal studies to lengthen life span.

Although water-only fasting over several days can be dangerous, fasting mimicking diets very low-calorie five-day eating plans that trick the body into thinking its fasting while allowing some foods and nutrients have been shown to be safer. Longo believes such diets will play a major part in maximising longevity.

Research continues on various fasting regimens. In a pre-print review, Matt Kaeberlein, a biogerontologist at the University of Washington, found limited evidence that avoiding food during specific windows of the day, without dropping overall calorie intake, increases life span in mice.

When calories are reduced, some genetic strains of mice seem to benefit, but others actually die faster. Calorie restriction could enhance longevity in some people while shortening lifespan in others, Kaeberlein wrote.

Were beginning to find faults with some extreme diets, Campisi said. The best approach, she said, is dietary restriction without malnutrition. The real benefit of fasting, she added, might simply come from losing weight.

Obesity is a risk factor for inflammation, and chronic, low-grade inflammation can accelerate ageing in a process known as inflammaging.

Sinclair eats just once per day, at dinnertime. When you eat is perhaps more important than what you eat, he said, referring to animal studies. Its easy to say mice arent humans, but there are some broad lessons.

EXERCISING, BUT IN MODERATION

Exercise can further simulate our ancestors stressful environments, some experts said, which can dupe your genes into extending your span of health. Just dont do too much.

In August, the Mayo Clinic published research suggesting an optimal amount of exercise: People who played sports for 2.6 to 4.5 hours per week since the 1990s were about 40 per cent less likely to have died than those who exercised less often.

Cardio workouts may extend longevity by multiplying mitochondria, the powerhouses within cells.

When scientists damage mitochondria in mice, the animals die faster, and mitochondrial dysfunction results in inflammaging in humans, Campisi said.

High-intensity interval training, or HIIT, may be particularly effective in adding to longevity.

K Sreekumaran Nair, a Mayo endocrinologist, found that 12 weeks of HIIT reversed many age-related differences in how older people synthesise proteins, buffering their mitochondria. Strength training may also partially reverse aspects of ageing.

As with fasting, just dont go overboard. Some young guys want to do too much of everything, Nair said. Theres no data that working out beyond a certain level gives you better mitochondria.

Being very aerobically fit may reduce mortality risk, but the August paper suggests a Goldilocks sweet spot; exercising more than 10 hours per week was linked to shorter life spans. Previous research has shown an association between extreme exercise and health problems, such as premature aging of the heart.

Nair suggests doing 35 minutes of HIIT three days per week; doing two non-consecutive days of strength training, focussing on core muscles, arms and legs, with three sets for each muscle group; and taking walks of 7,000 to 10,000 steps on the other two days. He also recommends trying to get at least three minutes of movement after every hour of sitting.

But keep in mind that these diet and exercise regimens cant magically undo a lifetime of mistakes. A young persons lifestyle will echo for decades, Sinclair warned.

BEYOND DIET AND EXERCISE

Sinclair noted another driver of longevity: Long-term, loving relationships. In a nearly 80-year study, researchers found that the most important factor in a long, healthy life was having a close partner.

Lynne Charnay, a 96-year-old actress who still performs onstage, attributes her longevity to marital bliss a double dose of it.

Ive had not one fabulous husband, but two! Boxing regularly with her personal trainer in New York doesnt hurt, either.

Another protective factor: Optimism. In 2019, Boston University psychologist Lewina Lee found that optimism was associated with exceptional longevity.

Take heart, Debbie Downers: Optimism can be cultivated through interventions. While optimism is about 25 per cent heritable, Lee told me, the rest is attributable to environmental influences. That may partly explain why people entrenched in poverty, with little reason for optimism, die at much younger ages.

But residents of lower-income areas also have limited access to the heathy foods and opportunities cited above.

Thats why experts on ageing have called for policies that improve access to healthy lifestyles, especially as findings about exercise, nutrition and other anti-ageing interventions continue to evolve, promising more years of health to those who can afford them.

Were still in the Wright brothers days of flight when it comes to longevity, Sinclair said. We still have a 747 and a Concorde to come, I hope, within our lifetimes.

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Adding healthy years to your life Borneo Bulletin Online - Borneo Bulletin Online

In a groundbreaking experiment, scientists hooked up a genetically modified pig kidney to a human patient and watched as the organ successfully filtered waste from the person's body.

The experiment was conducted in a brain-dead patient who was a registered organ donor and whose family granted permission for the procedure to be done, The New York Times reported. During the 54-hour experiment, the kidney remained outside the patient's body where the surgeons could observe the organ and take tissue samples. Although the kidney wasn't implanted inside the body, the procedure still allowed the team to see whether the organ would be immediately rejected; problems with animal-to-human transplants typically develop where the human blood interfaces with the animal tissue, such as in the blood vessels, experts told the Times.

Compared with primate organs, pig organs offer a number of advantages for transplantation. For example, pigs are already raised for food, produce large litters within a short gestation period and grow strikingly similar organs to humans', The Associated Press (AP) reported. But there's one major hurdle: Pig tissues carry a gene that codes for a sugar molecule called alpha-gal, which can send the human immune system into a frenzy and lead to organ rejection. (In people with a rare red meat allergy, alpha-gal can trigger life-threatening allergic reactions, Live Science previously reported.)

Related: How long can organs stay outside the body before being transplanted?

So in the transplant experiment, conducted last month, the team used a kidney from a genetically engineered pig that lacked this sugar-producing gene. To prepare the organ for transplant, the team modified the kidney in one additional way: they transplanted the pig's thymus, a small gland that helps train immune cells to fight infection, into the kidney, Dr. Robert Montgomery, who led the surgical team at NYU Langone Health, explained in a press conference held on Oct. 21.

Previous transplant studies in primates have hinted that, by moving the donor animal's thymus into a transplant recipient, this can help "reeducate" the recipient's immune system so the body accepts the transplant in the long-term, Montgomery said. That's why, in future, long-term trials with living participants, the team plans to use pig kidneys equipped with thymus glands, and that's why they used the same in this shorter experiment.

That said, for the 54-hour experiment, the team was watching out for a more immediate immune response against the kidney, where antibodies in the human blood supply attack the organ upon entry. But thankfully, no such attack took place, and instead, the kidney began producing large amounts of urine within minutes of being plugged into the patient's vessels.

"It had absolutely normal function," Montgomery told the AP. As soon as it was attached to blood vessels in the patient's upper leg, the pig kidney began filtering creatine, a waste product of muscle cell function, from the blood and quickly brought the creatine levels down to a normal range. "It didn't have this immediate rejection that we have worried about."

Given the promising results, the experiment could represent a big step forward for xenotransplants transplants from animals to humans but many questions remain.

"We need to know more about the longevity of the organ," Dr. Dorry Segev, a professor of transplant surgery at the Johns Hopkins School of Medicine who was not involved in the research, told the Times. Kidney rejection can occur long after a transplant "even when you're not trying to cross species barriers," so the durability of pig-to-human transplants will need to be carefully assessed, Dr. David Klassen, chief medical officer of the United Network for Organ Sharing, told the Times.

But if and when pig-to-human transplants can be cleared for wider use, "it's truly mind-boggling to think of how many transplants we might be able to offer," Dr. Amy Friedman, a former transplant surgeon and chief medical officer of LiveOnNY, a New York-based organ procurement organization, told the Times. Last year, 23,401 U.S. residents received kidney transplants, and currently, 90,240 Americans are on a waitlist for a kidney, the Times reported. Many patients with kidney failure can't qualify to get on a list, in part, due to the scarcity of available kidneys.

Pig kidneys could potentially make transplants available to many more people, but "you'd have to breed the pigs, of course," Friedman said.

Revivicor, a subsidiary of United Therapeutics, developed the genetically modified pig used in the recent transplant; the company's so-called GalSafe pigs were cleared for medical use and consumption by the U.S. Food and Drug Administration last year, the AP reported in December 2020. Revivicor has no immediate plans to sell the pigs as food, but the product could potentially be appealing to those with alpha-gal allergies, for instance.

In the future, the gene editing tool CRISPR could also make pig organ transplants safer, Live Science previously reported. Meanwhile, some labs are taking a very different approach to the transplant problem: growing human tissues and organs inside pigs so that they can later be harvested for transplants. In theory, because the organs would be made of human cells, they'd be less prone to rejection. However, the development of such human-pig chimeras is still in its early days and raises a number of ethical concerns.

Read more about the transplant experiment in The New York Times and The Associated Press.

Editor's note: This story was updated on Oct. 21 to clarify how the pig's thymus was used in the study, based on details shared by Dr. Robert Montgomery in a press conference held the same day. The original story was published on Oct. 20.

Originally published on Live Science.

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Pig kidney successfully hooked up to human patient in watershed experiment - Livescience.com

EXCLUSIVE: The host of 90 Day Bares All sat down with theGrio and opened up about her lengthy career

In an exclusive interview, Emmy award-winning journalist Shaun Robinson opened up about having longevity in the industry and 90 Day Bares All.

From her tenure on Access Hollywood to her Emmy winning coverage of A Grand Night in Harlem, Robinsons accomplishments speak for themselves. Since 2016, Robinson has also hosted the hit TLC series, 90 Day Fianc, with its new spin-off, 90 Day Bares All, currently streaming on Discovery Plus.

Robinson sat down with theGrio and opened up about the hit series, what the shows really say about relationships and couples, and her career in general.

Shaun Robinson attends Manuela Testolini And Eric Bent Present An Evening Of Music, Art And Philanthropy Benefiting In A Perfect World Honoring Prince Arrivals at The Jeremy Hotel on March 03, 2019 in West Hollywood, California. (Photo by Leon Bennett/Getty Images)

I think one of the reasons that I have lasted so long in the entertainment business is because I truly believe that my purpose is to help other people tell their stories, she shares exclusively with theGrio.

Speaking specifically to the 90 Day Fianc franchise, she explains, It has been so much fun being a part of the 90 Day Fianc franchise and 90 Day bares all. Ive been hosting the show for several years now and it keeps growing and growing and growing.

She even jokes that her own mother is a big fan of the reality TV series, saying, she is absolutely addicted to the show! Still, Robinson insists there is much more to the series than just entertainment, as there is plenty to learn about human behavior and relationships through the show.

All of these shows just really bring home the point that communication is the key to any good relationship. The couples that you see through their ups and downs, it always it always surprises me that they are able to talk about things that under normal circumstances, maybe they wouldnt say anything about, but we make them bring it all to the surface. They are really baring all.

Later in the conversation, Robinson opened up about her hard work in the news and entertainment business, and the secret to her longevity.

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I think that one of the things that contributes to my longevity is that I had the foundation of being a journalist, she shares. I studied journalism when I was in college and I knew that I wanted to be not just a talking head, but somebody who could really, you know, respect the art of journalism, because I do really think its an art, the integrity of journalism and working as hard as I could to be the best journalist that I could be.

Moderator Shaun Robinson onstage during Visionary Women present Grit, Guts, and Grace Lessons in Overcoming Adversity and Cultivating Resilience with Diana Nyad and Norma Bastidas at the Montage Beverly Hills on October 9, 2017 in Beverly Hills, California. (Photo by Rachel Murray/Getty Images for Visionary Women)

She adds, I truly believe that my purpose is to help other people tell their stories. So Ive worked really, really hard at it.

Check out Robinsons full interview with theGrio now.

New episodes of 90 Day Bares All drop Sundays on discovery+.

Have you subscribed to theGrios podcast Acting Up? Download our newest episodes now!TheGrio is now on Apple TV, Amazon Fire, and Roku. Download theGrio today!

The post Shaun Robinson on longevity and 90 Day Bares All appeared first on TheGrio.

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Shaun Robinson on longevity and 90 Day Bares All - Yahoo News

- Oral Presentation on In Vivo Gene Therapy Product Candidate and Data on Gene Editing Candidate Paved Way for Initiation of juMPStart and pheEDIT Trials -

BEDFORD, Mass., Oct. 20, 2021 (GLOBE NEWSWIRE) -- Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today presentations of nonclinical data and patient and caregiver feedback that support the Companys clinical programs for mucopolysaccharidosis type II (MPS II), or Hunter syndrome, and phenylketonuria (PKU). During the American Society of Human Genetics (ASHG) 2021 Virtual Meeting, an oral presentation included data from Homologys IND-enabling studies with HMI-203, a one-time, in vivo investigational gene therapy in development for the treatment of MPS II in the recently initiated Phase 1 juMPStart clinical trial. Patient and caregiver feedback on unmet medical needs in MPS II that informed trial design were also presented. Additionally, Homology shared results from a nonclinical study that demonstrated the precision of its nuclease-free, homologous recombination-based, in vivo gene editing candidate for PKU as the Company starts its first gene editing trial.

Our presentations at ASHG show the holistic approach we have taken to prepare for our Hunter syndrome gene therapy and PKU gene editing trials, demonstrating our commitment to thoroughly evaluating the product candidates and the needs of the patient community ahead of clinical studies, stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. Armed with patient and caregiver feedback on the unmet medical needs that persist, we recently initiated our juMPStart trial to evaluate a single-dose of HMI-203 in adults with Hunter syndrome. Additionally, integration assays from our in vivo PKU gene editing program demonstrated no evidence of off-target integration in human hepatocytes in a xenograft murine model and support our Phase 1 trial.

In the oral presentation titled, Long-Term Systemic Expression and Cross-Correction Ability of HMI-203: Investigational Gene Therapy Candidate for Mucopolysaccharidosis Type II or Hunter Syndrome, data showed that a single I.V. dose of HMI-203 in the MPS II murine model resulted in the following, through 52 weeks (end of study):

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Systemic expression of vector genomes, transcripts and functional I2S enzyme;

Secretion of active I2S into circulation demonstrating cross-correction;

Systemic reduction of disease-relevant biomarkers, including positive and significant correlation between cerebral glycosaminoglycan heparin sulfate (GAG-HS) and LAMP1 levels as well as cerebrospinal fluid (CSF) and cerebral GAG-HS levels; and

Prevention of progression of craniofacial and hindlimb deformities.

Also related to HMI-203, Patient-Focused Drug Development for a Single Intravenous Dose of HMI-203 Gene Therapy in Adult Mucopolysaccharidosis (MPS) II, or Hunter Syndrome, Patients included qualitative data on unmet medical needs from enzyme replacement therapy (ERT)-treated adult MPS II patients and/or their caregivers. They reported:

Weekly ERT infusions, surgeries and supportive therapies inadequately address range of motion and mobility, pain, and hearing loss;

Burdens associated with ERT and other therapies, including frequency and duration of treatment, and painful and extended recoveries;

High degree of anxiety regarding prognosis, longevity, need for more invasive surgeries, and financial challenges; and

Expectations for a potential one-time gene therapy include ability to maintain current quality of life with ERT independence.

To support HMI-103, its gene editing candidate for PKU, Homology also presented, Genome-Wide Integration Assay For rAAV Mediated Homologous Recombination (HR) in Human Hepatocytes Demonstrated Precision of In Vivo Gene Editing Approach. Using quantitative molecular methods, including long-read sequencing, in a murine liver model populated with human hepatocytes, a single I.V. dose of HMI-103 demonstrated on-target integration into the desired locus and no evidence of integration into any other genomic location.

For more information, please visit http://www.homologymedicines.com/publications.

About Homology Medicines, Inc. Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by addressing the underlying cause of the disease. The Companys lead clinical program, HMI-102, is an investigational gene therapy for adults with phenylketonuria (PKU) and additional programs focus on lysosomal storage disorders including Hunter syndrome, paroxysmal nocturnal hemoglobinuria (PNH) and other diseases. Homologys proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo through a gene therapy or nuclease-free gene editing modality, as well as to deliver one-time gene therapy to produce antibodies throughout the body through the GTx-mAb platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases. Homology believes its initial clinical data and compelling preclinical data, scientific and product development expertise, internal manufacturing capabilities and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit http://www.homologymedicines.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; the potential of our gene therapy and gene editing platforms, including our GTx-mAb platform; our plans and timing for the release of additional preclinical and clinical data; our beliefs regarding our manufacturing capabilities; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities of our manufacturing facility; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs as a result of operating as a public company. These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

Company ContactsTheresa McNeelyChief Communications Officer and Patient Advocatetmcneely@homologymedicines.com781-301-7277

Media Contact:Cara Mayfield Vice President, Patient Advocacy and Corporate Communications cmayfield@homologymedicines.com 781-691-3510

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Homology Medicines Announces Presentation of Data Supporting Clinical Programs in MPS II and PKU, including Nonclinical and Patient-Focused Research,...

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Summit will bring together over 40 leading experts in the field of psychedelics

Author of the article:

Toronto, Ontario(Newsfile Corp. October 21, 2021) Peak Human, an organization dedicated to helping people improve their lives using a proven blend of ancient knowledge and brand new technologies, is thrilled to announce the launching of Psychedelic Frontiers Virtual Summit.

Hoping to add to the growing conversation around psychedelic medicine, the Psychedelic Frontiers Virtual Summit will bring together over 40 leading experts shaping the role of psychedelics in our world. Taking place virtually from October 22 24, 2021 the summit will offer interviews with world renowned researchers such as Dr Robin Carhart-Harris, Dr. David Nichols, Dr. Matthew Johnson, and many more.

For a full list of speakers, see https://www.psychedelicfrontiers.ca

During the summit, hosts Dr. Sanjeev Goel and Neeraj Jain will bring you what you need to know to stay abreast of this rapidly evolving field. Learn how psychedelics are revolutionizing the treatment of mental health disorders and addictions, as well as how they are influencing society and culture for the better.

Psychedelics are about to change the worldagain! Were excited to put on this free summit to help educate people and bring attention to this very important development in mental health. Neeraj Jain

The event is sponsored by Circadian Wellness, Dimensions Health Centers, and Cubed Biotech Inc.

The event is free of charge to all attendees. To register and for more information, visit https://www.psychedelicfrontiers.ca

About the hosts:

Dr. Sanjeev Goel, MD, FCFP (PC) CAFCI

Dr. Sanjeev Goel is a practicing medical physician and the founder of Peak Human, a practice dedicated to helping his patients live 100x their potential NOW. He believes in a holistic approach to wellness as has done training in Anti-Aging, Integrative and Regenerative Medicine. He advocates a healthy lifestyle centered around plant based diet, focused physical activity and enhancing mental resilience. He also runs a medical cannabis clinic called Canadian MedCanna Clinics in Brampton, Ontario. Prior to Peak Human, he led the development of the largest patient health portal in Canada called midash and hosted the first ever Biohacker Summit in Toronto (Oct 2018) bringing culture, technology and health together. https://peakhuman.ca

Neeraj Jain, Psychedelic Investor

Neeraj is a serial entrepreneur and investor. He sold his first business in 2011. The company was named one of Profit Magazines fastest growing companies for three years in a row during his tenure. Neeraj has invested in ten startups to date, resulting in three successful exits thus far. Several of his recent investments are in the psychedelic space. Neeraj is passionate about health (mental and physical), longevity and science-based interventions. He is an active board member of several non-profits and charities. An electrical engineer by training, Neeraj started his career in aerospace and high-tech. He also holds an MBA with a focus on finance from Rotman School of Management.

About Peak Human:

Peak Human is based in the GTA (greater Toronto Area). It provides cutting edge health information and medical services globally to individuals who desire to be and stay in a Peak state. For Further information please email bepeak@peakhuman.ca or visit http://www.peakhuman.ca .

Contact: drgoel@peakhuman.ca neeraj@psychedelicfrontiers.ca

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To view the source version of this press release, please visit https://www.newsfilecorp.com/release/100534

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Peak Human Announces Launch of the Psychedelic Frontiers Virtual Summit - The Kingston Whig-Standard