It seems that this is a week for announcing significant progress in tissue engineering. You might recall that one of the groups involved in recellularization research transplanted a trachea into a human recipient a couple of years ago. The organ was from a donor, stripped of all its cells, and the remaining natural scaffold of the extracellular matrix repopulated with cells from the recipient. The end result was a transplanted organ that would not be rejected by the immune system. The same researchers have now gone one step further and successfully transplanted an entirely synthetic trachea grown from the patient's cells on an artificial scaffold - no donor organ required.

Surgeons have performed the first transplant operation using an organ wholly grown in a laboratory to give a man a new windpipe. The 36-year-old is recovering after surgeons implanted the world's first wholly lab-grown organ into his body.

...

Professor Paolo Macchiarini, a Spanish expert in regenerative medicine who led the groundbreaking operation, designed the Y-shaped synthetic trachea scaffold with Professor Alexander Seifalian, from University College London. The Y-shaped structure was made from a plastic-like "nanocomposite" polymer material consisting of microscopic building blocks. Two days after stem cells were placed into the scaffold they had grown into tracheal cells ready for transplantation. Since the organ was built from cells originating from the patient, there was no risk of it being rejected by his immune system.

In conjunction with lines of research like organ printing, this pace of work bodes well for the 2030s as a time in which failing or badly injured organs are no longer automatically fatal or the cause of lifelong disability for the young. There is still the question of how best to take advantage of this for the old, however: the frailty that comes with aging brings with it a much lower survival rate and success rate for major surgery - and any significant transplant is major surgery. Regrowth of organs alone is not the way to greatly extend the maximum human lifespan on a timescale that matters. Other technologies are needed as well:

There are many whole-body, multi-organ, or regional biochemical feedback and control loops in the body. There are types of age-related damage that involve the intracellular accumulation of biochemical junk - simply replacing cells doesn't get rid of that. If your only tool is bioprinting (which won't be the case, but let us think inside the box for a while here), then the solution to these problems starts to look like replacing more of the body at one time.

You can't just replace the brain, of course, which remains an important limiting factor and the real driving need for in situ repair technologies that operate at the level of cells, buildup of protein aggregates, and broken cellular machinery.

Altering cells used in tissue engineering so as to obtain a better result is a very viable prospect, as demonstrated in a recent investigation of tendon regeneration: "The basic function of tendon is to transmit force from muscle to bone, which makes limb and joint movement possible. Therefore tendons must be capable of resisting high tensile forces with limited elongation. ... the mechanical properties of tendons are related to the fibril diameter distribution, large fibrils could withstand higher tensile forces. ... In the healing tendon, a uniform distribution of small diameter collagen fibrils has been found with poorer mechanical properties than native tissue and shows no improvement of mechanical properties with time ... The present study for the first time demonstrated the use of a scaffold-free tissue engineered tendon model for investigating the biological function of collagen V in tendon fibrillogenesis. ... Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. ... These findings present a good example of in vitro tissue engineering model for tendon biology investigation and may provide basis for future development of cell or gene therapy for tendon repair."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119690/

A confirming review of studies: "Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting. ... A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. ... The results showed that shorter telomeres were significantly associated with cancer risk compared with longer telomeres. ... Studies have showed that telomeres are critical for maintaining genomic integrity and that telomere dysfunction or shortening is an early, common genetic alteration acquired in the multistep process of malignant transformation. In addition, telomere dysfunction has been found to be associated with decreased DNA repair capacity and complex [cellular] abnormalities. Both of animal studies and clinical observations have shown that shorter telomeres were associated with increased risk of cancers, such as epithelial cancers. However, telomere shortening might play conflicting roles in cancer development. For example, the progressive loss of telomeric repeats with each cell division can induce replicative senescence and limit the proliferative potential of a cell, thus functioning as a tumor suppressor. But, once telomeres reach a critical length, it will result in chromosome break, causing genome instability and enhancing potential for malignant transformation."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112149/

Publicity materials for a good-looking incremental advance from the tissue engineering community are doing the rounds in the press at the moment.

Researchers at The Saban Research Institute of Children's Hospital Los Angeles have successfully created a tissue-engineered small intestine in mice that replicates the intestinal structures of natural intestine - a necessary first step toward someday applying this regenerative medicine technique to humans.

...

Working in the laboratory, the research team took samples of intestinal tissue from mice. This tissue was comprised of the layers of the various cells that make up the intestine - including muscle cells and the cells that line the inside, known as epithelial cells. The investigators then transplanted that mixture of cells within the abdomen on biodegradable polymers or "scaffolding."

What the team wanted to happen did - new, engineered small intestines grew and had all of the cell types found in native intestine. Because the transplanted cells had carried a green label, the scientists could identify which cells had been provided - and all of the major components of the tissue-engineered intestine derived from the implanted cells. Critically, the new organs contained the most essential components of the originals.

The original paper is also available, for those who are interested. The normal caveats apply here - it's a promising advance for researchers to show that they can make lengths of intestine grow correctly inside a living mouse, using scaffolds seeded with cells. But bear in mind that this is only a demonstration: the new section of intestine isn't hooked up or being put under load. It'll be a few more years, I'd guess, before we see mice (or perhaps pigs) with tissue engineered and functional replacement small intestines.

If you'd like to learn more, I noticed an educational set of pages on the topic put up by the students at UCI:

In tissue engineering, there are two fundamentally different approaches that can be taken. The first is to replicate the organanatomically, with the expectation that the function of the engineered organ will therefore be the same. The second approach is simply to replicate its function. Researchers who aim to engineer intestine have adopted the anatomical approach with the key problems including the development of a muscular layer and neuronal innovation are major challenges to its success. On the other hand,if the aim is to develop an absorptive surface with neointestinal epithelium, it is possible to be more imaginative about how this can be achieved.

The fifth Strategies for Engineered Negligible Senescence (SENS) Conference, SENS5, draws closer. It will be held from 31st August to 4th September at Queens' College in Cambridge - so there's still time to register.

The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - to reverse - those changes, rather than merely to slow down their further accumulation. This broadly defined regenerative medicine - which includes the repair of living cells and extracellular material in situ - applied to damage of aging, is what we refer to as rejuvenation biotechnologies.

The program of presentations links to a range of interesting abstracts describing some of the important work that has taken place in the couple of years since SENS4, such as:

Tissue engineering of the liver using decellularised scaffolds

Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. ... The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic and biliary epithelial markers, thus creating a liver-like tissue in vitro.

MitoSENS: Allotopic expression of mitochondrial genes using a co-translational import strategy

The mitochondrion contains its own genome and encodes 13 proteins that are essential for the respiratory chain to function properly, [but] somatic mutations also accumulate in the mitochondria with normal aging. ... Thus far, we have stably transfected 5 of the 13 mitochondrial genes into the nuclear genome of human cell lines and are characterizing the expression and function of these exogenously expressed genes.

I also note that the group in Florida who are running a trial of granulocyte transplant therapy for cancer - based on the impressive results achieved by Zheng Cui - will also be presenting. On the whole, the program is well worth browsing. If you are interested in this field of science and biotechnology and you are not yet signed up for the conference, you should give some thought to attending.

Prioritizing the few exceptionally long-lived mammal species for full genome sequencing has been a few years in the making as a project, but I see that the researchers who initiated that effort have now completed the first item on their list:

Naked mole rat's genome 'blueprint' revealed

The industrious but unlovely naked mole rat is the latest creature to have its genome sequenced by scientists. A genetic blueprint for this bizarre-looking rodent could help researchers understand why it is so long-lived.

Scientists sequence DNA of cancer-resistant rodent

For the first time, scientists have sequenced the genome of the naked mole-rat to understand its longevity and resistance to diseases of ageing. Researchers will use the genomic information to study the mechanisms thought to protect against the causes of ageing, such as DNA repair and genes associated with these processes. To date, cancer has not been detected in the naked mole-rat. Recent studies have suggested that its cells possess anti-tumour capabilities that are not present in other rodents or in humans. Researchers at Liverpool are analysing the genomic data and making it available to researchers in health sciences, providing information that could be relevant to studies in human ageing and cancer.

Dr Joao Pedro Magalhaes, from the University of Liverpool's Institute of Integrative Biology, said: "The naked mole-rat has fascinated scientists for many years, but it wasn't until a few years ago that we discovered that it could live for such a long period of time. It is not much bigger than a mouse, which normally lives up to four years, and yet this particular underground rodent lives for three decades in good health. It is an interesting example of how much we still have to learn about the mechanisms of ageing. We aim to use the naked mole-rat genome to understand the level of resistance it has to disease, particularly cancer, as this might give us more clues as to why some animals and humans are more prone to disease than others. With this work, we want to establish the naked mole-rat as the first model of resistance to chronic diseases of ageing."

It will likely take a few years for the first interesting results to emerge from the genomic data - grants must be written, teams formed, studies carried out. Science, while fast, isn't yet instant. While researchers have a good idea as where in naked mole rat biochemistry they should be looking for both cancer resistance and longevity, molecular biology is an inordinately complex field of study. On the longevity side of the house, the composition of cellular membranes appears to be of greatest interest. You might look back into the Fight Aging! archives at these posts:

• Built Differently, Down in the Membranes
• Comparative Biology and the Membrane Pacemaker Hypothesis

The membrane pacemaker hypothesis predicts that long-living species will have more peroxidation-resistant membrane lipids than shorter living species.

Resistance to oxidative damage is of particular importance in mitochondria, cellular power plants that progressive damage themselves with the reactive oxygen species they produce as a byproduct of their operation - and that gives rise to a chain of further biochemical damage that spreads throughout the body, growing ever more harmful as you age. Less damage to the mitochondria should mean slower aging, and thus more resistant mitochondrial membranes should also mean slower aging.

Researchers have demonstrated that "damaged muscle tissues treated with satellite cells in a special degradable hydrogel showed satisfactory regeneration and muscle activity. Muscle activity in repaired muscle in a mouse model was comparable with untreated muscles. ... Satellite cells (SCs), freshly isolated or transplanted within their niche, are presently considered the best source for muscle regeneration. They are located around existing muscles. Hence, a patient's own cells can be used, from a muscle biopsy. ... A key issue for regeneration is how cells grow as a structure, as they usually require some form of framework. A hard framework would impede muscle growth and muscle cell penetration. The hydrogel, by contrast, provides a supportive structural skeleton but degrades quickly as muscle tissue returns and the support becomes unnecessary. The gel is initially liquid, hardens in place under UV light, and is easily penetrated by muscle cells. ... This is using the patient's own cells, without any lengthy culturing process, which means we could take a biopsy, produce the cells in a couple of hours, and implant them where needed - it can be done in theatre as one process. Using the patient's own cells eliminates any tissue rejection. ... The focus for initial clinical research in humans will be relatively small muscles at first, like deformities in the face and palate, or in the hand. It will be technically more demanding to grow larger muscles with more structure, which would require their own nerves and blood supply."

Link: http://www.ucl.ac.uk/news/news-articles/1103/31031101

The ability to make the immune system act in certain ways is the foundation for a range of powerful therapies: "scientists have discovered a way to wake up the immune system to fight cancer by delivering an immune system-stimulating protein in a nanoscale container called a vault directly into lung cancer tumors, harnessing the body's natural defenses to fight disease growth. The vaults, barrel-shaped nanoscale capsules found in the cytoplasm of all mammalian cells, were engineered to slowly release a protein, the chemokine CCL21, into the tumor. Pre-clinical studies in mice with lung cancer showed that the protein stimulated the immune system to recognize and attack the cancer cells, potently inhibiting cancer growth ... The vault nanoparticles containing the CCL21 have been engineered to slowly release the protein into the tumor over time, producing an enduring immune response. Although the vaults protect the packed CCL21, they act like a time-release capsule. ... [Researchers] plan to test the vault delivery method in human studies within the next three years and hope the promising results found in the pre-clinical animal tumor models will be replicated. ... The vault nanoparticle would require only a single injection into the tumor because of the slow-release design, and it eventually could be designed to be patient specific by adding the individual's tumor antigens into the vault ... The vaults may also be targeted by adding antibodies to their surface that recognize receptors on the tumor. The injection could then be delivered into the blood stream and the vault would navigate to the tumor, a less invasive process that would be easier on the patients. The vault could also seek out and target tumors and metastases too small to be detected with imaging."

Link: http://www.eurekalert.org/pub_releases/2011-05/uoc--usd042911.php

Accumulating damage to mitochondrial DNA is one of the causes of aging, and here researchers investigate its role in the aging of stem cells: "Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model [that suffered a greater rate of mitochondrial DNA damage], we demonstrate hematopoietic defects reminiscent of premature [stem cell] aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21549326

There's nothing you can do right now that will have a greater immediate effect on your life expectancy than exercise and calorie restriction. The best thing you can do for future improvement is to help researchers raise funds to develop repair technologies for human aging. But no-one wants to hear that. Everyone wants a silver bullet now, and it doesn't exist: "Friends occasionally ask me how they might best live healthy, longer. They inquire because I went to medical school, work in biotech, and focus professionally on developing drugs to treat diseases of aging by targeting aging genes. My response seems to surprise them, because it does not center on pharmaceutical products. The current answer on how to increase healthy human lifespan is simple: 'Eat less, and exercise more.' ... Modern medicine has discovered an impressive number of lifesaving new drugs for devastating diseases such as cancer, diabetes, heart disease, and infectious diseases. Nevertheless, for most of us, active lifestyles and less food will have a more profound effect than taking more medicines. Hard as it is, we should walk, run, and bike more, and reduce our food intake. The best way we can increase our chances to live healthy, longer is simple: eat less and exercise more."

View the Article Under Discussion: http://www.boston.com/bostonglobe/editorial_opinion/oped/articles/2010/07/05/a_simple_hard_answer_to_long_life/

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Investigating the biochemistry of aging in long-lived species and study of the impact of mitochondrial damage on aging are two quite distinct lines of research. They start to overlap on the matter of lipids, however, and the types and relative proportions of lipids that make up the membranes of cells and cellular components.

If you look back in the Fight Aging! archives, you'll find introductory entries on this topic:

You might recall that different fatty acid or lipid composition in cell membranes was floated as a reason for the ninefold longevity of naked mole-rats over related rodent species. Plenty of oxidative stress in the older mole-rats, but little sign of biochemical damage resulting from it - in comparison to those other rodents long since aged to death, that is. Better, more damage-resistant building blocks down at the molecular level might be the cause.

Better and more damage resistant building blocks: the mitochondrial free radical theory of aging paints mitochondria as the original source of damaging free radicals that react with and destroy cellular machinery - a process that ultimately contributes to age-related conditions such as atherosclerosis. If the machinery is more resistant to free radicals, then we would expect this contribution to aging to have a lesser effect, and thus lead to a longer life span.

If you dig further, you'll see that mitochondrial membrane damage is important in the mitochondrial free radical theory of aging, and the composition of mitochondrial DNA - the blueprint for the proteins that make up mitochondrial structure, such as the membranes - correlate strongly with species maximum life span.

I recently noticed an open access commentary that revisits this area of research:

Scientific investigation of mechanisms that determine lifespan can be divided into three general approaches. The first approach (the comparative method) began over a century ago comparing species differing greatly in maximum longevity and implicated a role for the speed of metabolism in determining the length of life

...

The recent insight from the comparative approach has been to link membrane fatty acid composition to maximum lifespan. This link grew from the finding that membrane fatty acid composition varied systematically with body-size among mammals and the suggestion this caused different cellular metabolic rates in mammals. Membrane fatty acid was then also linked to maximum lifespan (MLSP) variation among mammals. The reason why membrane fatty acid composition is correlated with MLSP is because fatty acids differ greatly in their susceptibility to lipid peroxidation.

Peroxidation of lipids in the body is effectively a form of damage: it is the reaction between a lipid and a free radical, changing the molecular structure of the lipid and rendering it unable to perform its assigned task in the cellular machinery of which it is a part. More resistant lipids means more damage-resistant mitochondria - and damage-resistant mitochondria should translate fairly directly into enhanced life span. So far the evidence supports this way of looking at matters.

That there is such a strong correlation between the building blocks of mitochondrial membranes and species life span is another strong sign that mitochondrial damage is very important in aging - and thus we should prioritize present efforts to support the development of biotechnologies that can repair or replace mitochondria throughout the body. These therapies are tantalizingly close to realization, but progress is slow and will remain slow until such time as funding and public interest are much larger than they are today.

A look at ongoing work on nerve regeneration in one laboratory: "One technology used [by] neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long. ... [Researchers] compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with [dorsal root ganglion neurons, or DRG cells], or with other cells known as Schwann cells. After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma. While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system's response to them. ... In a related line of research, [scientists] are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up."

Link: http://www.urmc.rochester.edu/news/story/index.cfm?id=3415

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Considerable scientific advances have been made in our attempt to understand the cause of aging over the past several decades. Although we do not yet know the basic causes of the aging process, we have learned enough to begin to apply some of the findings to people in an attempt to slow down or reverse some of the changes associated with aging.

At Longevity Achievement Center we are interested in applying discoveries made in basic sciences to maximize human life span function and potential. In addition, we wish to systematically prove that we are able to improve human functionality and extend human life span. For the foreseeable future, all anti-aging intervention therapy must be considered experimental. No matter what the treatment is, even if it is as simple as taking a Vitamin C pill daily, there is no proof to date that the treatments will extend life span. The necessary proof will come from experiments in which people are treated, then followed for many years, and then we can directly see if we have extended their life span. This will take a study of thirty to fifty years to prove. It would be very convenient if there were a way to measure a person's biological age and thereby test their biological age and then give them a treatment such as vitamin C for a period of one or two years and then measure their biological age again to see if their treatment made the person biologically younger. We can do this now with a battery of functional measures of performance. We know that they are predictive of increased performance and increased functionality, but we do not know if they are predictive of an increased life span.

We do not limit ourselves to the findings of conventional medicine. We are willing to draw on findings and techniques from alternative medicine as well. We have different participants, some who wish to have their parameters measured so that they can follow their deterioration throughout the years. They do not undergo treatment; They just get measured. Other people want modest treatment, improvement through diet, exercise, etc. Other people want controversial therapies such as hormone replacement therapy, chelation therapy, and cellular rejuvenation techniques. Some people wish to have some of their bodily cells preserved for future use in the rejuvenation techniques.

Some of the tests at LAC can be administered without enrolling in an entire program. These include:

Program I- Selective tests

Program II- Selective tests and defined intervention

Program III- Elite level, comprehensive testing and measurements to establish baseline, aggressive intervention and continuous monitoring over years.

Program IV- Storage and presentation of various cellular types such as fibroblasts, stem cells.

Our program encompasses diet, nutrition, vitamins, hormones, medicines, exercise, meditation, spiritual enhancement, improving social network and certain other experimental therapies. Every program is designed to meet an individuals specific needs.

Alternative Therapies >

Original post:
Longevity Medicine - The Sally Balin Medical Center ...

A recent presidential study has concluded that the carcinogens in the environment are contributing to high cancer rates.

As time goes on and on, more sources point to the fact that cancer is caused by carcinogens in the environment.  In fact, a new report was just released that was completed by a expert panel that currently advises Barack Obama. This panel, called the President’s Cancer Panel (or PCP), was set up in the 1970’s.

This 240 page report, which is available for the public to download, is called “Reducing Environmental Cancer Risk: What We Can Do Now.”  The report concludes that the known carcinogens in the environment are increasing, and they need to be dealt with by the government.

Dr. LaSalle D. Lefall, Jr. chairperson of the PCP stated, “There remains a great deal to be done to identify the many existing but unrecognized environmental carcinogens and eliminate those that are known from our daily lives – our workplaces, schools and homes.”  According to the report, people are exposed to up to 80,000 chemicals each day and many of them are completely unregulated.  These chemicals include radon, formaldehyde, and benzene.  Oftentimes people are completely unaware that they are being exposed to these cancer-causing chemicals.

The panel urged the government to take better steps to reduce people’s exposure to toxins by doing things like improving the understanding about these toxins, developing a better policy towards them and raising awareness. These are just a few of the suggestions made by the PCP.

The good news, however, is that researchers are learning more all the time about natural ways to treat cancer.  For example, exercise is an easy and effective way to fight cancer.  Additionally, turmeric is an extremely powerful herb that can actually kill cancer cells.  Turmeric contains the chemical curcumin.  Recent tests by the Cork Cancer Research Center show that curcumin can actually destroy cancer cells.

Sources:
news.bbc.co.uk
medicalnewstoday.com

Discuss this post in Frank Mangano’s forum!

From the Technology Review: "In a bid to harness the potential of embryonic stem cells, surgeons in California have implanted lab-grown retinal cells into the eyes of two patients going blind from macular degeneration. ... The two patients, whose names weren't released, are among the first volunteers ever to receive a treatment created using embryonic stem cells. ... We are excited about this treatment, because we think this has the potential to slow the disease progression. This company has had their ups and downs, and I am really happy to see they got into the clinic. We've had our fingers crossed. ... During a recent visit to Advanced Cell's laboratories, a research technician adjusted a microscope to show off the company's lead product: cube-shaped retinal pigment epithelial cells growing in a petri dish. Some were translucent, while others already had the brownish coloring of a mature cell. (The pigment absorbs stray light in the eye, acting as a kind of glare shield.) These retinal cells are the type that are killed off in macular degeneration, eventually leading to the death of photoreceptors, and the gradual loss of central vision. Advanced Cell believes that injecting new, lab-grown cells into the eye may cure the condition. ... It's no accident [that] both early studies of embryonic stem-cell therapies - those of Geron and Advanced Cell - involved cells of the nervous system. The reason is that embryonic stem cells naturally want to make neuroectoderm, a cell lineage in the embryo that forms the nervous system. ... Embryonic stem cells have a mind of their own, and they want to do certain things ... Efforts to produce other cell types, such as liver cells, have proved far more difficult."

Link: http://www.technologyreview.com/biomedicine/38030/

RasGrf1 is the gene associated with longevity in engineered mice with two female parents, and a deficiency in the gene achieved through other means boosts life span as well. Here is more theorizing on what it all means: "Interestingly, RasGrf1 is one of parentally imprinted genes transcribed from paternally-derived chromosome. Erasure of its imprinting results in RasGrf1 downregulation and has been demonstrated in a population of pluripotent adult tissues-derived very small embryonic like stem cells (VSELs), stem cells involved in tissue organ rejuvenation. ... downregulation of RasGrf1 in VSELs [protects] from premature depletion from adult tissues. Thus, the studies in RasGrf1-/- mice indicate that some of the imprinted genes may play a role in ontogenetic longevity and suggest that there are sex differences in life span that originate at the genome level. All this in toto supports a concept that the sperm genome may have a detrimental effect on longevity in mammals." So in summary, one of the ways in which RasGrf1 extends life seems to involve improvement in the capacity of stem cells in the older organism, and a significant effect on longevity can emerge from the contributions of one parent through the epigenetic imprinting process.

Link: http://impactaging.com/papers/v3/n7/full/100354.html

Organovo is the bioprinting startup whose investors include the Methuselah Foundation: "Organovo has been generating enough revenue from a series of new partnerships that [the company] put off an expected Series A venture round. ... the company has raised just over $2 million from private investors to develop 'bio-printing' technology that operates much like an inkjet printer. Instead of laying down ink, however, Organovo's bio-printer lays down a pattern of cultured cells and a jello-like hydrogel that supports the cells in a 3-D structure. In this way, Organovo already has been able to grow bio-engineered blood vessels, and to lay more ambitious plans to create kidneys, livers, and other vital organs in the same way. ... the work is still highly experimental, so getting regulatory approval to graft a bio-engineered blood vessel in a living patient will take years. In the meantime, [Organovo] found a burgeoning market among pharmaceutical companies by [creating] 3-dimensional 'constructs' of diseased or dysfunctional human cells that can be used as models for testing new drugs. Creating a 3-D matrix of cells enables each cell to interact with adjoining cells, so they react to drug compounds much as they would in the body. ... one of the pharmaceutical partnerships is with Pfizer to create 3-D constructs for drug discovery in two therapeutic areas. Organovo also is in talks with several additional partners ... One of the things that's been good about the past six months is that the promise of our technology is holding true. The constructs we're creating robustly build [blood vessels] with collagen, so the blood vessel grows stronger over time. The next challenge is getting to greater and greater vascularization of the construct. The emerging story is going to be, 'Who can make thicker tissues with more blood vessels inside?'"

Link: http://www.xconomy.com/san-diego/2011/07/13/organovos-bio-printing-technology-yields-unanticipated-revenue-from-pharma-partners/?single_page=true

At the Wall Street Journal: "At his lab in the Bronx, geneticist Nir Barzilai has spent more than a decade trying to unlock the biology of aging. His secret weapon: some of the New York area's oldest Jews. One of his major studies analyzes the genetic make-up and life habits of the oldest of the old: 500 physically and cognitively healthy individuals living well past the century mark. ... Research that began with some of the oldest New Yorkers is now set to spread throughout the U.S. Barzilai's work is the template for a ambitious national study to create a full sequencing of the genomes of 100 ethnically and geographically diverse centenarians. ... Barzilai's work seeks to improve the quality of life for the elderly. His research has found, to his surprise, that the 100-plus crowd has less than sterling health habits. As a group, they were more obese, more sedentary and exercised less than other, younger cohorts. ... Biologically speaking, what has allowed the centenarians in his study to live so long, even with life habits that often lead to disease and death in others? ... Barzilai and his team at Einstein's Institute for Aging Research have so far discovered three uncommon genotype similarities among the centenarians: one gene that causes HDL, good cholesterol, to be at levels two- to three-fold higher than average; another gene that results in a mildly underactive thyroid, which slows metabolism; and a functional mutation in the human growth hormone axis that may be a safeguard from age-related diseases, like cancer. He suspects there may be additional genotypes that scientists have yet to locate."

Link: http://blogs.wsj.com/metropolis/2011/07/13/in-the-science-of-aging-oldest-new-yorkers-hold-the-key/

Open Cures is an initiative aimed at speeding up progress along the best and most logical path for commercial development of demonstrated longevity-enhancing biotechnologies. Which is to say that they should be developed overseas, outside the reach of the FDA, and then accessed via medical tourism - just like all the cutting edge medical technologies that are available only outside the US, thanks to massive regulatory overkill.

Open Cures kicked off in earnest in May 2011, so this is still very much the stage of telling people about the idea and letting the community of potential supporters know that the initiative even exists. One part of that effort is a series of essays, the latest of which was published at h+ Magazine today under the title "Longevity Science Needs Documentation". Open Cures is a phased initiative, and the article is a deeper look at why Phase 1 of Open Cures involves the production of documentation - pulling out the best and most promising of present biotechnologies of longevity buried in research papers, and producing textbook quality how-to documents that are comprehensible to people who are not cutting edge researchers:

One of the challenging attitudes I've encountered of late is the idea that documentation of longevity science in this manner is largely worthless - that time and funds spent trying to make science clear to developers and laypeople should go towards other, more direct activities like further research. This sort of criticism is, I think, symptomatic of a failure to understand the necessary role of documentation in the broader scope of technological progress. This article, then, is an answer of sorts: what is the role of documentation, and why is it important enough to need dedicated organizations that do it well?

Read the whole thing, as the answer to that question isn't easily summarized in a single sentence - and that in and of itself is actually a part of the challenge. Complex ideas are hard to convey, and that fact places constraints on support for new technologies.

On the topic of producing documentation, you can see some of the early work in the Open Cures Wiki, such as a protocol outline for DIYbio participation in LysoSENS, and a similar protocol outline for mitochondrial protofection. For reference, a protocol is the name given to the step by step directions followed by a researcher or technician when carrying out a procedure in the laboratory. Both of these sketch outlines provide only the technical bare bones of their respective protocols, but are presently being expanded into full protocol documents, with the aim of producing textbook-quality publications.

Over the past few weeks, I've been working through oDesk to contract with biologists and biochemists around the world to work on these and other documents. It's an interesting business, and the global competition largely keeps the rates at an appropriate level for a volunteer initiative, even for writing that is fairly technical. My goal for the next few months is to acquire a reliable stable of writers this way, though this and similar services, and produce the first few high-quality protocols documents in full.

This involves a fair degree of learning and working through the pitfalls - but it should settle the questions of price and feasibility. So far it looks like there are a sufficient number of life scientists out there on these global contracting sites, some of whom can write decently well in addition to knowing their field. Also so far it looks like my initial guesses at the cost of producing documentation is not a million miles away from the reality - we'll see if that still holds once I'm into the next stage of finding artists to produce the necessary diagrams where openly available versions cannot be found.

In working with biologists scattered around the world, I've been greatly aided by those Open Cures volunteers willing to review and comment on works in progress. Many hands make light work, and while I've followed biotechnology for a number of years, I'm far from qualified to judge the contents of a protocol as accurate or not. I should also note that along the way, some other folk are also looking into producing informational documents on the state of medical tourism by country, and an early example of that sort of thing can also be found in the wiki.

Once this first stage of the first stage of the way and the Open Cures group has a set of completed protocols and writers ready to go, then it will be time to open things up to run a little faster: make the big list of documentation we'd like to have done in Phase 1, and push it into the sausage-making process of technical writing just as fast as it will go. That's about when I'll probably start soliciting funds and doing the rounds with cap in hand, but we'll see how that turns out.

The ability to use funding in and of itself requires some organization to set up: there's the legal side of the house, management and paperwork, and getting into the process to become a formally registered 501c3 charity. Fortunately some of the folk in the community are willing to help out on that front - it's "just" a matter of more time and energy put in that direction. Postponing it while the first stage of documentation is underway doesn't hurt, and in many ways it's better to put off the legal formalization of an initiative until you're sure that there's something there and that it's working the way you want it to.

So that's where things stand at the moment. Very early days yet, and lot yet to be accomplished.

An introductory open access review paper looks briefly at some of the theories of aging: "Ageing and senescence are related words and are often used interchangeably as both processes are characterized by progressive changes in the tissue of the body, eventually leading to a decline in function and death of the organism. Senescence refers to a post-maturational process that leads to diminished homeostasis and increased vulnerability of the organism to death. Ageing, in contrast, refers to any time-related process and is a continuous process that starts at conception and continues until death. The mechanisms involved in ageing are partially intrinsic to the organism, like genetic and epigenetic factors, and partially to the external origin, such as nutrition, radiation, temperature and stress. ... Various theories have evolved to improve our understanding of the ageing process so as to formulate strategies that enhance extension of life. The theories of ageing are classified based on the level at which the ageing mechanism is targeted: 1. Evolutionary theories, 2. Systemic theories, 3. Molecular and cellular theories ... Evolutionary theories state that ageing results from a decline in the force of natural selection. As evolution acts primarily to maximize reproductive fitness in an individual, longevity is a trait to be selected only if it is beneficial for fitness. Life span is, therefore, the result of selective pressures and may have a large degree of plasticity within an individual species as well as among species. ... In systemic theories, the ageing process is related to the decline of organ systems essential for control and maintenance of other systems within the organism. ... [Molecular and cellular theories] theories attempt to discern the mechanisms of ageing process at the cellular and subcellular levels."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125059/