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Category Archives: Human Longevity

The Future of Meat – Truthdig

Posted: November 23, 2019 at 11:56 am

The Meat Question: Animals, Humans, and the Deep History of Food

A book by Josh Berson

In the movie My Big Fat Greek Wedding, Aunt Voula, played by Andrea Martin, learns that her nieces fiance is a vegetarian. She says, He dont eat no meat?WHAT DO YOU MEAN HE DONT EAT NO MEAT? Oh, thats OK, thats OK, I make lamb!

Its funnyor is it? For those of us who eschew consuming animals and their byproducts, its hard to understand why most people today still enjoy eating flesh, seeing meat as something rather than someone. In The Meat Question: Animals, Humans, and the Deep History of Food, Josh Berson digs deep, literally, going back to the earliest times of human existence to find out when and how and why our relationship with animals as food began. The book considers three questions: 1) Did meat make us human? 2) Is growing affluence the cause of increased meat consumption? and 3) Will we see the end of meat?

As a vegan for 31 years and vegetarian for even longer, I rejoice with every new study or book published on the devasting impact that eating animals has on our health, quality of life and longevity. With hundreds and hundreds of scientific references, surely, I think, people will reduce or eliminate their meat consumption in order to reduce their risk of chronic disease. So many people have shared their stories in films, books and websites on how they reversed their heart disease or diabetes, achieved a normal weight, and regained their lives, by discovering a healthy, plant-based diet.

And yet, the consumption of animal flesh and animal byproducts continues to rise. The world population is projected to reach 9.6 billion by 2050 and people will be devouring more meat than ever before. There is no longer enough land mass on Earth to allow livestock to graze freely before slaughter. Today, the CAFO (concentrated animal feeding operation, AKA the factory farm) is the answer, but for the individual animals being raised in a CAFO for food, it is hell on earth.

What about the environment? As stinking lagoons of untreated livestock excrement are piled higher and deeper, surely we would realize our folly of raising tens of billions of animals for food. But no, it seems no amount of air and water pollution, greenhouse gas emissions, rainforest destruction, aquifer depletion, soil exhaustion, species extinction, etc. can curtail our desire for consuming flesh.

Click here to read long excerpts from The Meat Question at Google Books.

I have waited for decades for the discussion on climate change to heat up, for it to be considered for regulation in government policy and for it to headline mainstream news on a regular basis. Are we there yet? The late Robert Goodland, lead environmental adviser at the World Bank Group, wrote passionately and profusely about climate change and how we could all, simply and easily, prevent our demise by choosing plants instead of animals for food. Mitigating global warming by changing our diet was his plea, because it would buy us time to transition our factories and modes of transportation to sustainable energy sources.

Was his message heard? Do we have the capacity to hear this message?

Berson acknowledges the devastating impact on health, environment and animals due to meat consumption very briefly, early in his books prologue. He writes as if we all know this information already, no need to elaborate in detailalthough he does paint the nightmarish image of current reality, transporting cattle from Australia to China by air! We use all our best inventions, concentrating cattle into airplanes to satisfy the gluttonous desire for flesh while making a nice profit. Is no thought made of the reckless use of energy resources or abundant release of greenhouse gas emissions in this scenario? We have created our own little shop of horrors at home on Earth, responding to the escalating cry, Feed Me!

Are we who we areare we humanbecause we eat meat? To address the first question, Berson presents to us a dry and academic history of humankind. This is not easy reading. As we travel to periods 1 million to 5 million years ago, the text is riddled with archeological terms that even an above-average reader would not be familiar with. It takes patience to comprehend it all, moving back and forth through ancient and unfamiliar times.

Berson explains that our evolutionary history was a result of our diet versatilitybeing able to find and consume a variety of plant and animal-based foods, available in different periods and locations. Berson addresses the tenuous relationship between the consumption of meat and the evolution of human brains:

Where do we get the energy to run our big brains? Over the past twenty-five years, this has been a key question in evolutionary anthropology. For many observers, our expensive brains represent exhibit A in the case for meats role in human evolution. Meat, the argument goes, supported encephalization [the evolution of large brains] [But] the brain cant do much with the energy in meat. The brain relies on glucose as its primary fuel the energy in the lean meat of wild ungulates is mainly in the form of protein. The body has a limited capacity to convert amino acids into sugars. Protein does not represent a sustainable source of energy for the maintenance of nervous tissue.

Berson goes on to explain that energy is not the sole expense of the human brain, which is 50% to 60% lipid by dry mass. DHA (omega-3 docosahexaenoic acid) is vital in supporting the high lipid content of our brains. DHA can be hard to find in human dietsits primary direct source is aquatic foods. It can, however, be synthesized from alpha-linolenic acid (LNA). [C]linical evidence indicates dietary LNA represents a more-than-adequate source of DHA for the growth and maintenance of the central nervous system, Berson writes. Where are the terrestrial dietary sources of alpha-linolenic acid? Its highly concentrated in chloroplast membranes, so leafy green plants represent a strong source, as do mosses, the fatty tissue of herbivores that consume these things, and the usual range of oilseeds, including flax, hemp, and walnuts.

He concludes, Meat may well have played a role in buffering the vagaries of access to a higher-quality diet in early humans. But it wasnt because it was essential to brain development. Nor is meat essential to how we eat in the future.

Later in the book, we arrive in the present day. Here, we can scrutinize our history more carefully as the abundance of evidence improves resolution. Question 2 is addressed: Is growing affluence the cause of increased meat consumption? To balance Western influence dominating the telling of human history, Berson writes, I offer an Asia-Pacific perspective on the modern meat economy. My aim is to nudge the food systems literature away from the North Atlantic and toward those parts of the world whose tastes, expertise, and climate will dominate global patterns of change in diet over the next two or three generations. We learn that affluence alone does not drive the demand for meat. Rather a complicated economic and political system has been created that forces those disempowered, impoverished individuals to choose the convenience of cheap meat because they have no access to affordable alternatives.

Berson writes, Until we recognize that marginalized humans and animals raised under industrial conditions occupy coordinate roles in a single system of economic violence, we will make no progress unworking meats power.

In the epilogue we learn that Berson has been a vegetarian for 25 years and a vegan for 19, except for a handful of exceptions. He admits his original motivation was unclear but over time it was about reducing his footprint: I wanted to limit my claim on the Earths resources to levels that would allow the largest number of people to enjoy the quality of life that I took for granted. He began to question his reasons for being vegan after about a decade, which became the motivation for this book. The dispassionate tone throughout is intentional; Berson desired to present information as objectively as possible, without judgment that might alienate the reader.

Will we ever see the end of meat? The author believes if humanity survives, its possible that few if any animals will be on our plate. After reading The Meat Question, I have a better understanding of why it is not effective to use single issue arguments like health, environment, climate change and animal cruelty to convince people to reduce or eliminate their animal consumption:

To imagine a world in which humans no longer get any part of their subsistence from animals is to imagine a world where the bond of economic necessity, of precariousness, between humans and animals has been succeeded by a bond of mutual regard, among humans and on the part of humans for other living things. This is a more radical vision than that which underlies arguments for the cessation of meat eating on grounds of health, or carbon footprint, or animal sentience.

Berson shows us how to think about eating animals in broader terms. Gambling on food prices with agricultural derivatives and investing in agricultural land acquisitions negatively impact the access to adequate food. Meat consumption is one piece of a complex and violent capitalist system.

There was one question I couldnt help but ask myself while reading The Meat Question: Are humans naturally violent? Berson concludes with this question as well, asking whether human beings are fundamentally cruel, condemned to reduce one another to lumps of meat. He acknowledges that if we dont want to accept systemic violence as our reality, a divergence will be required, in diet among other things, as radical as any we have experienced before.

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30-year-old Harvard study on longevity: Five daily habits to follow for a healthy living – Republic World – Republic World

Posted: at 11:56 am

Scientists at Harvard have reportedly been studying human anatomyfor years. From researching about how to eat healthy to studying what goes on inside our body, they know it all. Recently, they came up with research which discovered the 5 rules an individual should follow to lead a healthy life. The study done by Havard is 30-year long study which gives 5 rules one should compulsorily follow:

Also Read:Healthy Diet: Benefits Of Protein And Fiber In Your Diet

The Lancet stated that 1 in every 5 death globally is associated with a p[oor diet. It is believed that we consume double the recommended amount of processed meat which affects our body causing obesity and other body-related diseases. The Havard T.H Chan School of Public healths study found out that adding enough fruits, nuts, whole grains, fruits and vegetables can lower the risk of heart attack stroke by 20 per cent.

Exercising regularly is something every dietician or nutritionist might suggest. According to the World Health Organization, People who are not active enough have 20-30 per centincreased their risk of death. Experts in this field have advised that a healthy adult should exercise for 150 minutes every week.

Also Read:Eye Health And Eyesight: 5 Best Foods To Include In Your Diet

A good diet and exercising regularly helps you maintain a healthy weight. The United Nations study has found out that around 800 million people around the world are obese and the number has tripled since 2016.

It is recommended to not intake too much of alcohol. The taste of wine has been found to engage the brain than any other human behaviour. The Scripps research institute found that an ingredient in red wine can also help to reduce stress but it should be consumed in moderation, preferably justa glass or two. Nature claimed that a moderate amount of wine can be beneficial and too much alcohol is a health risk.

Also Read:Food Combinations That May Sound Weird And Gross But Taste Delicious

Smoking is injurious to health and every individual is aware of it. If a person quits smoking, within a year of quitting smoking, your risk of heart disease drops by half. After 10 years, the risk of lung cancer falls by 50 per cent, as claimed by the World Health Organization. Giving up smoking also reduces the chance of impotence and infertility among people who wish to be parents. WHO also found that maintaining these healthy habits add 12 years of life for men and 14 for women.

Also Read:Fitness Tips: Indoor Exercises That You Can Do To Stay Healthy And Fit

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What the termite mound ‘snowmen’ of the NT can tell us about human nature – The Conversation AU

Posted: at 11:56 am

The Stuart Highway in the Northern Territory is dotted with around 300 termite mounds, dressed as people. They are reminiscent of giant, ochre coloured snowmen in their distinctly human forms of decoration.

These tall, colourful mounds variously sport scarves, caps, singlets, shirts, sunhats, bras, hard hats and even a beer can. They start just below Darwin, near the Noonamah Hotel, and occur all the way down to Kulgara, just north of the South Australian border. This covers around 1,800 kilometres.

The snowmen are an irreverent, larrikin, Northern Territorian phenomenon. But who created them? And what can they teach us about fundamental human behaviours?

Termite mounds occur naturally. They are made of clay, soil, sand and other natural materials, bound together with the saliva of termites. They occur globally and can reach as high as five metres.

In the NT, the first snowmen appeared during the 1970s. More quickly followed. They appear on both public and private land, lining major highways and rural roads and extending into national parks.

Over the years, many people have made these snowmen. Some were made by roadworkers, staying at roadside camps along the highway, with limited access to towns and entertainment but plenty of work clothing. Some were made by the owners of rural and remote properties. Some were made by fisherman traversing to remote fishing locations. Some may have been decorated by tourists.

The manager of the Royal Flying Doctor Service Tourist Facility, Samantha Bennett, is a Territorian born and bred. She says of the mounds:

Sometimes the clothing is changed according to festive calenders. They dont do Halloween, but they definitely do Christmas and Australia Day. They dress them up with flags and high viz clothing, which is cool because you can see them from a distance. Sometimes, they are used to help with directions. They mark the location of a driveway in a remote area or turnoffs to secret fishing spots.

The snowmen are actually snow people men, women and children. Some are arranged in family groups. Gender is marked by clothing. Economic status can be discerned through the use of silk scarves, resort wear or hard hats.

The NT has the highest rate of beer drinking in Australia. Not that long ago, it had the highest rate of alcohol consumption in the world. Perhaps unsurprisingly then, beer cans are held by some snowmen.

The snowmen are part of a wider cultural landscape in the NT. If you go to the Coburg Peninsula and lose one of your thongs, you put the remaining thong on the thong tree: a tree covered top to bottom with old rubber thongs.

Then there is the fence of shame on Andreas Avenue at Dundee Beach, west of Darwin. This is where you put your fishing rod if you have broken it during your trip.

There is material evidence that the snowman tradition has some longevity. In some cases, the clothing is in a dilapidated state. In others, the termites have renewed their building efforts on top of the clothes.

It is unlikely that the snowmen were created by Aboriginal people. As Barunga resident Isaac Pamakal explains: Aboriginal people dont do that, because that might make people sick.

Termite mounds are woven into NT Aboriginal belief systems. In some areas, there is a belief that anyone who knocks over a mound will get diarrhoea. Indeed, powerful Indigenous people have been known to put someones clothes onto a termite mound in order to make that person sick. The intended victim would be identified by the sweat on their clothing (which contains their DNA). (This link between sweat and DNA is an example of Indigenous science, which is increasingly being drawn on.)

However, termite mounds are mostly known, in the NT and around the world, for their medicinal properties. They contain high proportions of kaolin, used for the treatment of gastric-disorders in both traditional and modern pharmacologies.

Francoise Foti has conducted research in two NT Aboriginal communities, Nauiyu Nambiyu (Daly River) and Elliott. She records people consuming small quantities of termite mounds to deal with gastric disorders or after eating certain foods like yams, turtle or goannas. Similarly, termite mound material is sometimes eaten during pregnancy or lactation as it contains iron and calcium.

The urge to humanise inanimate objects is a global phenomenon through both time and space. For thousands of years, humans have had a penchant for making animals and things look like people.

This is most clearly shown in a style of rock art known as therianthropes, which depicts beings that have both human and animal characteristics. It also manifests in depictions of mermaids, centaurs and other mythical creatures.

So while they are special, the snowmen of the NT are not unique. They are simply another example of a human need to reinvent the world in our own image.

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Breakthrough Gene Therapy Clinical Trial is the World’s First That Aims to Reverse 20 Years of Aging in Humans – PRNewswire

Posted: at 11:56 am

MANHATTAN, Kan., Nov. 21, 2019 /PRNewswire/ -- Libella Gene Therapeutics, LLC("Libella") announces an institutional review board (IRB)-approved pay-to-play clinical trial in Colombia (South America) using gene therapy that aims to treat and ultimately cure aging. This could lead to Libella offering the world's only treatment to cure and reverse aging by 20 years.

Under Libella's pay-to-play model, trial participants will be enrolled in their country of origin after paying$1 million. Participants will travel to Colombia to sign their informed consent and to receive the Libella gene therapy under a strictly controlled hospital environment.

Traditionally, aging has been viewed as a natural process. This view has shifted, and now scientists believe that aging should be seen as a disease. The research in this field has led to the belief that the kingpin of aging in humans is the shortening of our telomeres.

Telomeres are the body's biological clock. Every time a cell divides, telomeres shorten, and our cells become less efficient at dividing again. This is why we age. A significant number of scientific peer-reviewed studies have confirmed this. Some of these studies have shown actual age reversal in every way imaginable simply by lengthening telomeres.

Bill Andrews, Ph.D., Libella's Chief Scientific Officer, has developed a gene therapy that aims to lengthen telomeres. Dr. Andrew's gene therapy delivery system has been demonstrated as safe with minimal adverse reactions in about 200 clinical trials. Dr. Andrews led the research at Geron Corporation over 20 years ago that initially discovered human telomerase and was part of the team that led the initial experiments related to telomerase induction and cancer.

Telomerase gene therapy in mice delays aging and increases longevity. Libella's clinical trial involves a new gene-therapy using a proprietary AAV Reverse (hTERT) Transcriptase enzyme and aims to lengthen telomeres. Libella believes that lengthening telomeres is the key to treating and possibly curing aging.

Libella's clinical trial has been posted at the United States National Library of Medicine (NLM)'s clinicaltrials.gov database. Libella is the world's first and only gene therapy company with a clinical trial posted at clinicaltrials.gov that aims to reverse the condition of aging.

On why they decided to conduct its project outside the United States, Libella's President, Dr. Jeff Mathis, said, "Traditional clinical trials in the U.S. can take years and millions, or even billions,of dollars. The research and techniques that have been proven to work are ready now. We believe we have the scientist, the technology, the physicians, and the lab partners that are necessary to get this trial done faster and at a lower cost in Colombia."

Media Contact:Osvaldo R. Martinez-ClarkPhone: +1 (786) 471-7814Email: ozclark@libellagt.com

Related Files

curing_aging_booklet.pdf

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william-bill-andrews-ph-d.jpg William (Bill) Andrews, Ph.D. Dr. Bill Andrews is a scientist who has spent his entire life trying to defeat the processes that cause us to age. He has been featured in Popular Science, The Today Show, and numerous documentaries on the topic of life extension including The Immortalists documentary.

Related Links

Dr. Bill Andrews speech at RAADfest 2018 (Sept 21, San Diego, CA)

bioaccess: Libella's CRO partner in Colombia.

SOURCE Libella Gene Therapeutics, LLC

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UN spotlights digitization of audiovisual archives to preserve human history on World Day – UN News

Posted: October 27, 2019 at 3:36 pm

Audiovisual documents contain the primary records of the history of the 20th and 21st centuries, enabling us to pass down common heritage across generations, however, the moving pictures and radio sounds capturing our collective pasts run the risk of vanishing through decay, or being lost to time as the technology once used to handle them becomes obsolete.

The theme of this years World Day, Engage the Past Through Sound and Images praises the expertise of the people working to safeguard collections of the past for generations to come, which without, large portions of our cultural heritage would disappear to be lost forever, the UN said on the Day.

In 2005, the United Nations Education, Scientific and Cultural Organization (UNESCO) approved commemoration of the Day every 27 October, at its biennial meeting of Member States to spotlight the need for urgent conservation measures of important audiovisual files-a parallel effort to the entitys establishment of theMemory of the World Programme, in 1992, which made clear that significant audiovisual collections worldwide suffered a variety of detrimental fates.

War, looting and dispersal, illegal trading, and preservation funding shortfalls are a few of the burdens that have threatened precious archive holdings for centuries.

For material still intact, digitizing physical records has been a method of escaping inevitable wear and tear from decades of handling, and extending the longevity of audiovisual libraries.

UNESCO in 2015 launched a fundraising project to create digital surrogates of the Organisations archives dating back to its predecessors, including the League of Nations International Institute for Intellectual Cooperation.

The institutional archives and historical audiovisual collections contain evidence of more than 70 years of ideas and actions for peace and international understanding that span the Organizations wide-ranging fields of competence.

Three years on, the Organisations Paris headquarters began housing a digitization lab for material to be more efficiently sorted, digitized, quality checked, and made available online.

A wealth of 5,000 photos, 8,000 hours of sound recordings, 45 hours of film, and 560,000 pages of governing body documents capture oceanography, space exploration, human rights communications, and traces of intellectual figures such as Marie Curie, Albert Einstein, Masaharu Anesaki and more.

Clickhere to experience the online library thus far.

UNESCO's Director-General, Audrey Azoulay, said the Day marks an occasion "to remember the importance of audiovisual materials for connecting with our history and understanding who we are today."

"The past century was marked by unprecedented human development and world-shaping events. We must ensure its lessons are transmitted to future generations", she urged.

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Can we predict the future? Bill Gates says yes, in this one area – CNBC

Posted: at 3:36 pm

When Bill Gates gave the 2019 Professor Hawking Fellowship Lecture at Cambridge University on Oct. 7, he answered a question posed by Stephen Hawking in his final book, "Brief Answers to the Big Questions": Can we predict the future?

"I believe the answer is yes we can" when it comes to the future of health, Gates said.

"I'm lucky that my work gives me a view of all the amazing discoveries in the works right now," said Gates. "That's why I'm able to predict the future."

Gates has made global health his priority, funding research and solutions for some of the world's largest health epidemicsvia the Bill and Melinda Gates Foundation.

So what does that future look like? Based on the technology innovation he sees, here are three of the predictions Gates made about the future of health.

Hundreds of millions of adults and children around the world suffer from some form of malnutrition, according to the World Health Organization.

But according to Gates, through understanding the role of the microbiome, or the "good bacteria" in the body, and in particular in the gut, malnutrition can be solved.

"We've learned a lot about [the microbiome] in recent years, and will continue to learn more over the next two decades," Gates said during the lecture. "That deeper understanding is why I predict we're going to solve malnutrition."

For example, Gates predicts that "we'll be able to create next-generation probiotic pills that contain ideal combinations of bacteriaeven ones that are tailored to your specific gut."

In addition, he also predicts the creation of "microbiota directed complementary foods," which would be consumed to help digest food, protect from infection and help the microbiome.

Gates says that understanding how the gut gets "messed up" and how to fix the microbiome will not only help end malnutrition, but also other diseases, including asthma, allergies and some autoimmune diseases.

"If we can figure nutrition outand I believe we will within the next two decadeswe'll save millions of lives and improve even more," Gates said.

Malaria kills 435,000 people around the world each year, according to the World Health Organization.

However, "promising new developments" in mosquito control (which is more effective at fighting malaria than trying to vaccinate or treat it, according to Gates) lead him to believe "we'll have virtually eliminated malaria by 2040," he said.

"For one thing, we finally know where the mosquitoes are," Gates said, which allows more targeted anti-mosquito efforts. Gates also cited gene-editing to eliminate malaria-carrying types of mosquitoes while leaving the others so as not to disrupt the ecosystem.

Gates said the focus of healthcare will shift over the next 20 years to improving lives, rather than just saving lives.

"It seems like a subtle difference, but it has a huge impact on how you approach healthcare," Gates said. "Within two decades, I believe every country on earth will be able to focus on not just keeping you alive but healthy and well."

As the number of preventable deaths around the world decline, which he predicts will happen as problems like malnutrition and diseases like malaria are eradicated, healthcare priorities can shift focus.

"The shift from longevity to wellness doesn't just change how we approach healthcare," he said. "It unlocks all sorts of amazing opportunities for people and societies to thrive."

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Thinking about death: High neural activity is linked to shorter lifespans – Big Think

Posted: at 3:36 pm

If there's one thing that humans can't stop thinking about, it's death. But new research published in the journal Nature suggests that all that thinking might be the very thing that brings death on.

More precisely, researchers discovered that higher neural activity has a negative effect on longevity. Neural activity refers to the constant flow of electricity and signals throughout the brain, and excessive activity could be expressed in many ways; a sudden change in mood, a facial twitch, and so on.

"An exciting future area of research will be to determine how these findings relate to such higher-order human brain functions," said professor of genetics and study co-author Bruce Yankner. While it's probably not the case that thinking a thought reduces your lifespan in the same way smoking a cigarette does, the study didn't determine whether actual thinking had an impact on lifespan just neural activity in general.

To say this was an unexpected finding is an understatement. We expect that aging affects the brain, of course, but not that the brain affects aging. These results were so counterintuitive that the study took two additional years before it was published as the researchers gathered more data to convince their reviewers. Yankner was forbearing about the delay. "If you have a cat in your backyard, people believe you," he said. "If you say you have a zebra, they want more evidence."

Yankner and colleagues studied the nervous systems of a range of animals, including humans, mice, and Caenorhabditis elegans, or roundworm. What they found was that a protein called REST was the culprit behind high neural activity and faster aging.

First, they studied brain samples donated from deceased individuals aged between 60 and 100. Those that had lived longer specifically individuals who were 85 and up had unique gene expression profile in their brain cells. Genes related to neural excitation appeared to be underexpressed in these individuals. There was also significantly more REST protein in these cells, which made sense: REST's job is to regulate the expression of various genes, and it's also been shown to protect aging brains from diseases like dementia.

But in order to show that this wasn't simply a coincidence, Yankner and colleagues amplified the REST gene in roundworm and mice. With more REST came quieter nervous systems, and with quieter nervous systems came longer lifespans in both animal models.

Zullo et al., 2019

Normal mice (top) had much lower levels of neural activity than mice lacking the REST protein (bottom). Neural activity is color coded, with red indicating higher levels.

Higher levels of REST proteins appeared to activate a chain reaction that ultimately led to these increases in longevity. Specifically, REST suppressed the expression of genes that control for a variety of neural features related to excitation, like neurotransmitter receptors and the structure of synapses. The lower levels of activity activated a group of proteins known as forkhead transcription factors, which play a role in regulating the flow of genetic information in our cells. These transcription factors, in turn, affect a "longevity pathway" connected to signaling by the hormones insulin and insulin-like growth factor 1 (IGF1).

This longevity pathway has been identified by researchers before, often in connection with possible benefits to lifespan from fasting. Additionally, the insulin/IGF1 hormones are critical for cell metabolism and growth, features which relate to longevity in obvious ways.

The most exciting aspect of this research is that it offers targets for future research on longevity, possibly even allowing for the development of a longevity drug. For instance, anticonvulsant drugs work by suppressing the excessive neural firing that occurs during seizures, and in studies conducted on roundworms, they've also been shown to increase lifespan. This recent study shows that this connection might not be coincidental. Similarly, antidepressants that block serotonin activity have also been shown to increase lifespan. Dietary restriction has long been implicated in promoting longer lifespans as well. Dietary restriction lowers insulin/IGF1 signaling, which this study showed affects the REST protein and neural activity. More research will be needed to confirm or reject any of these possibilities, but all represent exciting new avenues to explore, possibly resulting in the extension of our lifespans.

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Does the human lifespan have a limit? – Varsity Online

Posted: at 3:36 pm

How many of us will see our 100th birthdays?DoD photo by U.S. Navy Petty Officer 2nd Class Kayla Jo Finley/Released

The maximum lifespan of an organism varies significantly between species, ranging from a single day for mayflies, to several hundred years for Greenland sharks. While the goal for most organisms at an evolutionary level is to reproduce, humanity continuously aimed at increasing our lifespan. Life expectancy is used as an indicator of a countries development, as well as a measure of social and scientific progress. A longer life would permit us to spend more time having valuable life experiences, make crucial contributions to our fields of work, potentially helping humanity progress further as a species.

Recent medical advances allow us to further pursue this quest. The average life expectancy in the U.K. is around 81 years currently significantly higher than the 35 years it was in the 17th century. We now live in an era of diseases of old age, where degenerative disorders such as dementia are dubbed the biggest health crisis of our time in developed countries. This poses an important question are our bodies biologically capable of sustaining the lifespans we strive for, or are we being overly ambitious?

Research into longevity is extremely complex and controversial. We only know of 48 people in history who have lived past the age of 115. It was already hypothesised in 1825 that mortality rates increase exponentially with age, implying that human life expectancy must tend towards a maximum value. A 2016 study claimed that even with a perfectly healthy lifestyle and access to medical interventions when necessary, the natural biological human age limit is approximately 115, with only a few individual outliers, in part due to their genetic architecture. This would imply that regardless of the technology we develop, it should be unable to increase our life expectancy past this limit.

This is a plausible suggestion when we consider ageing on a cellular level. The Hayflick limit refers to the number of times that most cells divide before entering senescence. Hayflick (currently a UCSF Professor of Anatomy at 91 years of age) proposed this theory in the 60s, after finding that a human cell population could only divide between 40 to 60 times in culture before entering senescence. Elizabeth Blackburn, Carol Greide and Jack Szostak went on to win a Nobel prize in 2009 for their discover that this correlates with telomeres (repetitive sequences of DNA at the ends of chromosomes that protect them) being reduced to a critical length, since these shorten after each cell division.

We only know of 48 people in history who have lived past the age of 115

Even if the body did not undergo any other processes of ageing, the accumulation of senescent cells would eventually cause death. Almost all senescent cells either self-destruct or are destroyed by the immune system, though a small number remain and have a strong signalling effect which can lead to chronic inflammation or disruption of nearby tissues and potentially even stimulate surrounding cells to become senescent. These processes are thought to be linked to the development of numerous age-related diseases, including Alzheimers and Type II diabetes. It appears that regardless of the condition the body is kept in, degenerative conditions will inevitably catch up with everyone.

Recent investigations carried out in Italy by observing lifespans of over 3,000 individuals over the age of 100 have revealed that annual mortality risks plateau by the age of 115 at around 50%. This is likely because any age related disorders that were to occur would have set in by this point. As a majority of diseases is associated with increasing age, we need to better understand what is driving ageing. We may be able to, through a mixture of medical, lifestyle, and environmental interventions push our life expectancy up.

But what about going further than, say, 115 years? While the early attempts at extending telomeres (using the enzyme telomerase) caused cells to become cancerous, more recent efforts using more controlled delivery systems are more promising at increasing lifespan without the added cancer risk. Promising results have recently arisen in the form of research carried out by the Spanish National Cancer Centre.

It could be possible for us to alter our susceptibility to the degenerative effects of age

The telomeres of mice embryonic stem cells were elongated beyond normal levels, and mice developing from these stem cells were generated. These mice had a 12.8% increase in median longevity, and an 8.4% increase in maximum longevity, compared to mice with normal telomere length. The mice also underwent less DNA damage as they aged, and showed lower cholesterol and LDL levels, as well as improved glucose and insulin tolerance.

Such research demonstrates that it could be possible for us to alter our susceptibility to the degenerative effects of age. Much remains to be discovered at what governs the rate of ageing, and then, whether reductions in the rate of ageing actually translate to longer lifespans, or simply to better health along the lifespan.

While many questions remain concerning the upper bound on lifespan, much could be done to increase life expectancy right now. In the last 100 years, the increase in life expectancy can be attributed to factors such as effective immunisation programs, antibiotics and public health initiatives around hygiene and sanitation. While life expectancies may appear to be approaching a plateau, many believe that developments in fields such as artificial intelligence and genetics could be responsible for our next surge in life expectancy by improving the ways in which we deliver healthcare. Some claim that it does not matter if our bodies degrade if we are able to develop technologies such as prosthesis and bionics.

While extending lifespan may seem like an exciting concept, this may pose additional challenges on both a societal and personal level. For instance, we are already struggling as a planet with overpopulation and its associated consequences, such as carbon emissions. Increased life expectancy has played a role in the development of this problem and may continue to do so. Many countries, such as Japan, have an aging population individuals aged 65 and older in Japan make up a quarter of its total population, estimated to increase to a third by 2050. Therefore, the dependency ratio (the proportion of workers to non-workers) creates a need for more efficient social care provision and strategies. .

Ageing is a natural process, and it may not necessarily be possible to halt the clock. As a species, we seem to have more control over how long we live than many other species do. In modern society, it is becoming increasingly more likely that excess of food or age related degenerative disorders will kill us rather than starvation or disease. However, if we do strive to push our life expectancies to new limits, it is vital that we consider the challenges this will pose for our bodies and society.

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200 years of history show us how to measure happiness – Quartz

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How do you measure happiness? The answer to this question has eluded philosophers, scientists, and researchers for years. As happiness is a subjective feeling, its difficult to find a way of objectively measuring it. One of the most common methods for measuring happiness is through self-report surveys and polls, such as the UNs World Happiness Report uses.

But when it comes to understanding how our happiness ranks when compared to previous generations, researchers have had an equally difficult time finding methods to measure it. Academics studying the past usually use a method called close readinga thoughtful, critical analysis of a textwhich allows them to gain a deeper understanding of how authors might have been feeling at the time they wrote these texts. Psychologists have confirmed this, and know that what a person says or writes can often reveal much about their underlying happiness.

But what if you could read every book that was ever written in order to develop an understanding of what it was really like to live through the last 200 years of history?

My colleagues and I recently conducted research that has taken a first step towards developing a quantitative picture of happiness throughout history. We developed a method that was able to analyze online texts from millions of fiction and non-fiction books and newspapers published over the past 200 years.

We did this by applying a statistical algorithm to millions of digitized historical texts in order to understand how happy writers were at the time of writing. This is called sentiment analysis, which measures how frequently an author uses positive and negative words to express their emotional attitude. More positive words, like love, happiness, and celebration indicate more positive feelings, whereas more negative words like death, anger, and sadness indicate negative feelings.

As some words have changed their meanings over time, we also took this into account when analyzing words and their meanings. For example, words like gay and risk have changed their valence over timein this case, both becoming more negative.

By analyzing the language used in written texts from four Western countriesthe UK, US, Italy, and Germanywe were able to create a quantitative picture of historical subjective well-being, which we called the National Valence Index.

The National Valence Index is able to compute the relative levels of happiness or unhappiness by looking at the language used in any text in any given year. By comparing this against the Eurobarometer survey data on subjective well-being, our measure appears to be reasonably reliable. We then use the National Valence Index to look at how wars, and economic and health changes over the last 200 years have impacted overall happiness.

What we found was remarkable. While gross domestic product (GDP) is often assumed to be associated with a rise in well-being, we found that its effect on well-being throughout history is marginal at best. GDP has increased fairly consistently over the last 200 years in the four countries that we looked at, but well-being has moved up and down dramatically over that time.

What is perhaps most remarkable is that well-being appears to be incredibly resilient to short-term negative events. Wars create dramatic valleys in well-being, but soon after the war well-being frequently recovers to its pre-war levels. Lasting changes to our measure of happiness occur slowly, over generations.

Our study found that Germany is at its happiest in the 1800s, and just after World War II. Similarly high values are also found in the other nations during the 1800s. However, these values might not be entirely accurate, as writers during the Victorian Age were typically of a higher class, and the topics they wrote about and language they used was different to now. Germany, however, has seen a rise in subjective happiness since the 1970s.

In the UK, the Winter of Discontent, in the late 1970s, is the lowest point of well-being and happiness we measured, which began to fall during the 1950s. The nation was happiest during the interwar years in the 1920s, and at the end of World War II.

In the US, happiness was affected by events such as the Civil War, the Great Depression, and the Korean War. The US was happiest in the 1920s, before the Great Depression and World War II caused well-being to plummet.

Italy was similarly affected by the world wars, but has seen a steady increase in subjective well-being since the 1970s.

These findings allow governments to better understand how they should form policies. For example, how should governments spend their money to improve happiness?

Across countries, an extra year of life (in terms of longevity) is equivalent to a 4.3% rise in GDP. A year of internal conflict is equivalent to a 30% drop in GDP. Policies that seek to enhance longevity, for example through providing better access to healthcare throughout life, may therefore be better than policies that only attempt to increase GDP, which is increasingly being challenged as a measure of progress.

The National Valence Index might also be used to understand how rising national debt and unemployment will influence our happiness in the future. A better understanding of what things positively and negatively effect societys happiness could have measurable effects on both quality of life and a nations economic output. More generally, understanding our psychological past can help us to better envision a positive psychological future.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Vulnerability of the industrialized microbiota – Science Magazine

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One world, one health

As people increasingly move to cities, their lifestyles profoundly change. Sonnenburg and Sonnenburg review how the shift of recent generations from rural, outdoor environments to urbanized and industrialized settings has profoundly affected our biology and health. The signals of change are seen most strikingly in the reduction of commensal microbial taxa and loss of their metabolic functions. The extirpation of human commensals is a result of bombardment by new chemicals, foodstuffs, sanitation, and medical practices. For most people, sanitation and readily available food have been beneficial, but have we now reached a tipping point? How do we conserve our beneficial symbionts and keep the pathogens at bay?

Science, this issue p. eaaw9255

The collection of trillions of microbes inhabiting the human gut, called the microbiome or microbiota, has captivated the biomedical research community for the past decade. Intimate connections exist between the microbiota and the immune system, central nervous system, and metabolism. The growing realization of the fundamental role that the microbiota plays in human health has been accompanied by the challenge of trying to understand which features define a healthy gut community and how these may differ depending upon context. Such insight will lead to new routes of disease treatment and prevention and may illuminate how lifestyle-driven changes to the microbiota can impact health across populations. Individuals living traditional lifestyles around the world share a strikingly similar microbiota composition that is distinct from that found in industrialized populations. Indeed, lineages of gut microbes have cospeciated with humans over millions of years, passing through hundreds of thousands of generations, and lend credence to the possibility that our microbial residents have shaped our biology throughout evolution. Relative to the traditional microbiota, the industrial microbiota appears to have lower microbial diversity, with major shifts in membership and functions. Individuals immigrating from nonindustrialized to industrialized settings or living at different intermediate states between foraging and industrialization have microbiota composition alterations that correspond to time and severity of lifestyle change. Industrial advances including antibiotics, processed food diets, and a highly sanitized environment have been shown to influence microbiota composition and transmission and were developed and widely implemented in the absence of understanding their effects on the microbiota.

Here, we argue that the microbiota harbored by individuals living in the industrialized world is of a configuration never before experienced by human populations. This new, industrial microbiota has been shaped by recent progress in medicine, food, and sanitation. As technology and medicine have limited our exposure to pathogenic microbes, enabled feeding large populations inexpensively, and otherwise reduced acute medical incidents, many of these advances have been implemented in the absence of understanding the collateral damage inflicted on our resident microbes or the importance of these microbes in our health. More connections are being drawn between the composition and function of the gut microbiota and alteration in the immune status of the host. These relationships connect the industrial microbiota to the litany of chronic diseases that are driven by inflammation. Notably, these diseases spread along with the lifestyle factors that are known to alter the microbiota. While researchers have been uncovering the basic tenets of how the microbiota influences human health, there has been a growing realization that as the industrial lifestyle spreads globally, changes to the human microbiota may be central to the coincident spread of non-communicable, chronic diseases and may not be easily reversed.

We suggest that viewing microbiota biodiversity with an emphasis on sustainability and conservation may be an important approach to safeguarding human health. Understanding the services provided by the microbiota to humans, analogous to how ecosystem services are used to place value on aspects of macroecosystems, could aid in assessing the cost versus benefit of specific microbiota dysfunctions that are induced by different aspects of lifestyle. A key hurdle is to establish the impact of industrialization-induced changes to the microbiota on human health. The severity of this impact might depend on the specifics of numerous factors, including health status, diet, human genotype, and lifestyle. Isolating and archiving bacterial strains that are sensitive to industrialization may be required to enable detailed study of these organisms and to preserve ecosystem services that are unique to those strains and potentially beneficial to human health. Determining a path forward for sustainable medical practices, diet, and sanitation that is mindful of the importance and fragility of the microbiota is needed if we are to maintain a sustainable relationship with our internal microbial world.

Aspects of lifestyle, including those associated with industrialization, such as processed foods, infant formula, modern medicines, and sanitation, can change the gut microbiota. Major questions include whether microbiota changes associated with industrialization are important for human health, if they are reversible, and what steps should be taken to prevent further change while information is acquired to enable an informed cost-versus-benefit analysis. It is possible that a diet rich in whole foods and low in processed foods, along with increased exposure to nonpathogenic microbes, may be beneficial to industrial populations.

The human body is an ecosystem that is home to a complex array of microbes known as the microbiome or microbiota. This ecosystem plays an important role in human health, but as a result of recent lifestyle changes occurring around the planet, whole populations are seeing a major shift in their gut microbiota. Measures meant to kill or limit exposure to pathogenic microbes, such as antibiotics and sanitation, combined with other factors such as processed food, have had unintended consequences for the human microbial ecosystem, including changes that may be difficult to reverse. Microbiota alteration and the accompanying loss of certain functional attributes might result in the microbial communities of people living in industrialized societies being suboptimal for human health. As macroecologists, conservationists, and climate scientists race to document, understand, predict, and delay global changes in our wider environment, microbiota scientists may benefit by using analogous approaches to study and protect our intimate microbial ecosystems.

Ecosystems change. Seasonal or periodic fluctuations may occur over short time scales, trajectories of lasting change can occur over time, and sudden perturbations can result in instability or new stable states. Ecosystems can also reach tipping points at which biodiversity crashes, invasive and opportunistic species take over, and the services expected of the original ecosystem are lost, which may result in further damage and/or extinctions. Each human is an ecosystem composed of thousands of species and trillions of members, the host body of Homo sapiens being just one of those species. Most of these community members are microorganisms that reside in the gut, which is the focus of this article. Sequencing of the microbiota shows that human microbiomes are composed of a stunning array of species and functional diversity. An intricate set of interactions, just now being mapped, connects microbial species within a microbiota to one another and to human biology and is beginning to show how profoundly these microbes influence our health.

The first steps in human microbiota assembly occur upon birth, with microbes vying to colonize environment-exposed surfaces in and on the body. This process is influenced by many factors, including mode of birth, nutrition, environment, infection, and antibiotic exposure (1, 2). Specific taxa of microbes have codiversified with Homo sapiens, consistent with vertical transmission over hundreds of thousands of generations (3). The millions of years of association have provided ample opportunities for our biology and theirs to coevolve (4).

Intimate connections between the microbiota and the human immune system, nervous system, and metabolism have been revealed over the past decade (59). The specific microbes that first colonize the infant gut and the ensuing succession of the community can irreversibly influence mucosal and systemic immune development (10). Orchestrating the assembly of a health-promoting gut microbiota or manipulating a mature community to alter human physiology has vast therapeutic potential, which has captured the attention of the biomedical community. Beyond the importance of the microbiota to human health, recent research has also demonstrated its vulnerability. This ecosystem is susceptible to change by selective forces (11, 12). For example, a single course of one type of antibiotic can decimate and reshape the gut microbiota (13). Exciting research is racing to identify disease treatments using microbiome manipulation, but less focus has been placed on how to protect the microbiota from damage that may be deleterious to human health (14).

The germ theory of disease, formalized in the 1860s by Louis Pasteur, portrayed microbes as an enemy to be controlled and eradicated. The subsequent war on microbes deploying hand washing, sterile surgical techniques, and antibiotics has saved countless lives. In 1900, pneumonia, tuberculosis, and infectious enteritis were the three leading causes of mortality in the United States, accounting for almost one-third of all deaths (15). By the end of the millennium, these infectious disease killers were replaced by chronic diseases, including heart disease, cancer, and stroke, which offered evidence of our ability to effectively manage germs. However, the inverse relationship of infectious and chronic disease rates may share a similar underlying cause. Consistent with tenets of the hygiene hypothesis, limited exposure to microbes may result in defects in immune function and/or regulation, leading to an increasing burden of allergic and autoimmune diseases. In light of our new knowledge about the role of the microbiota in health, the war on microbes likely needs to be reconsidered in less combative terms. The profound success of germ-killing techniques and drugs developed in the past century that have minimal acute side effects has led to overuse. The rise of superbugs that are resistant to antibiotics and chemical bactericides reveals that there is a cost to our war on microbes (16). However, the longer-term and less obvious costs to human health of disrupting the microbiota may come from chronic metabolic and immune diseases. Although intimate, the communities that live in our guts are hard to study, and at present we do not fully understand the health impact of the differences in the microbiota observed between human populations.

Microbiota composition, diversity, and gene content in industrialized peoples vary substantially from that of more traditional rural populations and likely from that of our ancient ancestors, indicating that aspects of our lifestyle are changing our resident microbes (4, 1720). Antibiotics are not the only potential contributor to this effect. Other recent changes in practice, including Caesarean section (C-section) delivery, infant formula, and consumption of industrially produced foods, have all been shown to influence the gut microbiota of humans (2123). Although these technological and medical advances have had undeniable benefits (especially for emergency health care), their implementation and widespread use have occurred without an understanding of their impact on our resident microbial communities. At one extreme, microbiota shifts coincident with industrialization may have no impact (or even a beneficial impact, for example, by removing or reducing microbes with pathogenic potential) on human health and longevity. At the other extreme, the microbiota alterations observed in industrialized populations may be a major contributor to the misregulation of the human immune system that drives chronic inflammation (4, 24). Noncommunicable diseases (NCDs), such as stroke, heart disease, some cancers, chronic kidney disease, diabetes, and dementias, all of which are fueled by chronic inflammation, are associated with the worldwide expansion of industrialized lifestyles and are predicted to create a global health crisis in the coming century (25, 26).

In many ways, the rapid changes experienced by the microbiota of urban humans are analogous to those observed in macroecosystems throughout the world (27). Over time and with tremendous efforts to generate and analyze data, a global scientific consensus has emerged that human-induced climate change will have a devastating impact on Earths species and ecosystems if not curtailed and reversed (28, 29). Likewise, as we become increasingly cognizant of the importance of the microbiota in dictating the duration and extent of our health, it is vital that we reframe our relationship with microbes and use strategies similar to the sustainability and biodiversity conservation efforts under way around the globe. What steps should we take now to protect resident microbes, given the current data and range of possible outcomes?

That the gut ecosystem would change in response to marked lifestyle alterations is not surprising. What is notable is that the microbiota of traditional populations share taxa that have been lost or reduced in individuals living in the industrialized world, which we have termed VANISH (volatile and/or associated negatively with industrialized societies of humans) taxa (Fig. 1A) (30). A study comparing the industrialized microbiota with that of three Nepalese populations living on a gradient from foraging to farming showed the shift in microbiota composition that takes place as populations depart from a foraging lifestyle (31). Intermediate states of lifestyle change toward urbanization are accompanied by less extreme but evident changes in the microbiota (Fig. 1, B and C).

(A) Aggregation of gut microbiota composition from multiple studies separated by principal component analysis of BrayCurtis dissimilarity of 16S rRNA enumerations [adapted from Smits et al. (33)]. Top panel: The first principal component explains 22% of the variation in the data from 18 populations living lifestyles spanning from uncontacted Amerindians in Venezuela (top) to fully industrialized populations in Australia, the United States, Canada, and Ireland (bottom). Bottom panel: Mapping the relative abundance of bacterial families on PCo1 reveals global patterns in the VANISH taxa, which are associated negatively with industrialized societies, and BloSSUM taxa (bloom or selected in societies of urbanization/modernization), such as the Bacteroidaceae and Verrucomicrobia. (B) Heat map adapted from Jha et al. (31) displaying taxa that change across lifestyles in one geographic location (Nepal) of individuals living as foragers (Chepang), settled foragers (Raute, Raji), or agriculturalists (Tharu) versus industrialized individuals in the United States. (C) Model adapted from Jha et al. (31) of strain loss and/or reduction versus gain and/or increase across a lifestyle gradient. Different patterns of changing abundance correspond with specific aspects of lifestyle that change as populations move away from foraging and toward urbanization. The model could also reflect the historical progression of industrialized humans from foraging (Homo sapiens arose ~200,000 to 300,000 years ago) to agriculture (starting 10,000 to 20,000 years ago) to industrialization (starting 100 to 200 years ago).

Similarly, a longitudinal study of individuals immigrating from a Thai refugee camp to the United States showed a loss of VANISH taxa within months of immigrating (32). The longer the immigrants lived in the United States, the more profound the changes. In addition to changes in microbial membership, functional differences in the microbiota correspond to lifestyle. Traditional populations such as the Hadza, a hunter-gatherer group living in Tanzania, like the immigrants from Southeast Asia, harbor microbiota with a larger and more diverse collection of carbohydrate active enzymes (CAZymes) than their industrial counterparts. CAZymes digest complex plant polysaccharides, characteristic of traditional dietary fiber intake (32, 33). By comparison, the microbiota of U.S. residents are enriched in CAZymes that degrade host mucus, which serves as a backup food source for gut microbes when dietary fiber is limited, a hallmark of the industrialized diet (33, 34). The selection of mucus-utilizing bacteria in industrialized populations is evident in the enrichment of Akkermansia muciniphila (a mucin-loving bacterium in the phylum Verrucomicrobia) that was found in a worldwide comparison of industrialized and nonindustrialized microbiomes (Fig. 1A) (33). Whether the loss or reduction of VANISH taxa cause or contribute to the growing burden of NCDs in humans remains to be determined. However, determining the potential importance of VANISH taxa to human biology will require efforts to maintain their diversity before it is lost (35, 36).

We must not forget how the attempted eradication of pathogenic microbes with antibiotics, increased sanitation, and medicalized birth has saved countless lives. Other features of industrialized life, such as the Western diet and infant formula, have added convenience, increased human productivity and met the food demands of a growing population. The development and widespread implementation of these technological advances occurred before there was an understanding of their effect on the microbiota and the significance of the microbiota to human health. One difficulty in understanding the effects of different aspects of industrialization on the human gut microbiota is that so many lifestyle factors covary. Below, we summarize studies that have sought to disentangle facets of the industrialized lifestyle that change the microbiota.

The development and use of antibiotics have accompanied human population growth, industrialization, and rapid technological advances. Antibiotics have become the prototypic factor associated with industrialization that negatively affects the gut microbiota. Antibiotic resistance and increased susceptibility to enteric pathogens are well-known negative effects of antibiotic use. Accumulating data also show that oral antibiotic use has long-term effects on the composition of the gut microbiota (37). Just 5 days of ciprofloxacin was shown to decimate the gut microbial community, which only recovered slowly over the ensuing weeks and months (13). Recoveries were individualized, were incomplete, and differed in their kinetics (13). Similarly, other studies have shown that antibiotics can have a long-term impact on the microbiotaperhaps we should not be surprised because most of these medicines were originally designed to have broad-spectrum effects (38).

For most of human existence, humans consumed food and water laden with microbes, some of which caused disease. But humans also routinely consumed benign bacteria, both through incidental environmental exposure (e.g., from dirt or unsanitized food or on the skin) and from fermented foods (39). The recent shift to consuming largely sterile food and water has likely also influenced the microbiota. For example, the source of drinking water was significantly associated with microbiota composition in the cross-sectional study of Nepalese individuals living on a lifestyle gradient, as well as the Hadza (31). As industrial populations removed microbes from drinking water, the burden of diseases such as cholera and other waterborne illnesses decreased. Recent studies in mice suggest that sanitization in the form of cage cleaning does exacerbate extinctions in the microbiota after perturbation (40). The industrialized human microbiota also bears the hallmarks of sanitation, showing greater interindividual differences in microbiota composition (an indication of less microbe sharing between people) compared with traditional human populations in Papua, New Guinea, where individuals share more bacterial species with one another (20). Risking increased infectious diseases by reducing standards of sanitation would be misguided, but a better understanding of how hygienic practices shape our microbiota and the resulting impact on human health is needed. Restoring the consumption of nondisease-causing microbes may ameliorate diseases that are common among populations that consume sterile food and water (41).

Antibiotics and sanitation are intended to limit exposure to pathogenic microbes, but other practices such as the Western diet and C-section births that are not targeted at microbe control may nevertheless be having a profound effect on the microbiota.

Diet is a major driver of the composition and metabolic output of the microbiota (4244). Humans have shifted from a diet of exclusively wild animals and gathered foods to one of domesticated livestock and agricultural produce (10,000 to 20,000 years ago) to a more recent shift to industrially produced foods, including chemically managed livestock and produce and sterilized, ultraprocessed foods containing preservatives and additives (45, 46). These shifts have resulted in a food supply capable of supporting a growing human population, but perhaps at the cost of the populations health (47).

One notable change to foodstuffs is the unintentional depletion of a major form of sustenance for the microbiota: microbiota-accessible carbohydrates (MACs; the complex carbohydrates found in the dietary fiber of edible plants such as legumes, whole grains, vegetables, nuts, etc.) (42). A high-MAC diet was commonplace when humans exclusively foraged for nutrition, and low-MAC diets have been associated with lower microbiota diversity and poor markers of health in humans and in animal models (4850). The paucity of MACs in the industrialized diet was compensated for by additional protein, simple carbohydrates, and fat, which had the effect of altering the composition and functional output of the microbiota (43, 51). The use of additives such as emulsifiers and non-nutritive sweeteners is pervasive in industrialized food. Both have been shown to alter microbiota composition and promote intestinal inflammation. In addition, emulsifiers promote adiposity and non-nutritive sweeteners alter the metabolic output of the microbiota toward one that resembles that of type 2 diabetics (21, 52).

Small changes to the microbiota have the capacity to amplify over generations. For example, mice fed a low-MAC diet showed reduced microbiota diversity that compounded over generations. Restoration of a high-MAC diet was not sufficient to regain microbiota diversity, which indicated that species within the microbiota had gone extinct during the four-generation length of the experiment (50). In another study, antibiotic treatment of pregnant mice altered the microbiota of the offspring and resulted in metabolic derangement that predisposed the pups to diet-induced obesity (53). Similarly, C-section delivery in humans results in colonization of the infant with microbes derived from skin instead of the mothers vaginal microbiota (54). Acute perturbations from diet, antibiotics, and medical practices could have been propagated over generations and synergized with heightened hygiene and sanitation to result in the population-wide ecosystem reconfigurations observed today. The effects of other factors associated with an industrialized lifestyle on the microbiota, including increased sedentary behavior, stress, exposure to new chemicals (e.g., plastics, herbicides, and pesticides), and social isolation, have only begun to be explored (5557).

It is not a given that the microbiota found in traditional populations, which likely shares more commonality with that of our ancient ancestors, would improve the health of a person living in an industrialized society (4). For example, several members of a traditional gut microbiota, such as parasites, are frank pathogens. Some functions of a traditional microbiota may have beneficial effects in the context of a traditional lifestyle but may not in a more urbanized context. We have simplified these points and recognize that some parasites may confer benefits to human health, but how benefit is defined may depend on context and the individual. For example, parasites that protect against intestinal inflammatory diseases may cause opportunistic infections in immunocompromised individuals (58).

While remaining agnostic about broad connections between change in the microbiota and human health, it is worth considering underlying evolutionary principles that might predict whether microbiota changes are likely to be beneficial, deleterious, or neutral. A very conservative view is that until we have a good understanding of which microbes or communities are beneficial or deleterious, including how context determines this answer, we should recognize that (i) our resident microbes have the potential to affect our health in profound ways and (ii) individual lifestyle and/or medical choices and population-level lifestyle, medical, and dietary choices can change these communities. Similar to early, albeit insufficient, steps to address climate change before the full scope of the problem was understood, such as developing renewable alternatives to fossil fuels, a hedge against potential catastrophe seems warranted. In the case of our gut microbes, acting to minimize unintended loss of biodiversity is likely a wise strategy until we know more. We discuss possible strategies below.

An important question is whether loss or reduction of resident, codiversified microbes and associated functions could have a negative health impact on humans. Some properties of the human microbiota appear to have been stable during much of human evolution before industrialization. It is expected that the combined biology and genome of the human body and its commensal microorganisms would have coevolved to maximize human reproductive success (fitness) during that time (59). Because industrialized humans are interested in a long, healthy life, it is worth asking whether long life is consistent with the reproductive success of early humans. The reproductive success of modern hunter-gatherers corresponds to being long lived (as demonstrated by evidence supporting the patriarch hypothesis); therefore, the components of the microbiome that lived within humans throughout most of our existence as a species likely promote biology consistent with a long, healthy life (60).

From the microbial point of view, a bacterial species is chiefly concerned with making more of itself. Therefore, it is worth considering whether it is possible for members of the microbiota that increase host health and longevity to arise. In other words, the question is not only whether the interests of host and microbiota are aligned (i.e., to promote a long, healthy life of the host), but whether microbes that promote the health and longevity of their hosts are retained and favored over evolutionary time.

Gut-resident microbes that improve host health and life span are most likely to arise when the health-promoting function does not incur a short-term fitness cost to themselves (61, 62). For example, imagine a microbial pathway that not only generates energy for the microbe by fermenting a dietary complex carbohydrate but also produces a fermentation end product that can be absorbed by the host and play beneficial metabolic and/or regulatory roles. These microbes would contribute to host health without incurring a fitness cost and could be selected over time as a result of host fitness, longevity, and transmission to offspring and other individuals. We might expect that loss of these coevolved microbes and associated functions would have a negative health impact.

The industrialized microbiota could be considered better adapted to an industrialized host lifestyle by harboring more resistance to antibiotics and being less proficient at dietary fiber degradation. However, such a microbiota may not be optimized for our health.

Learning how to minimize harm to an ecosystem is an easier prospect than rebuilding one that has deteriorated; however, the realization of an ecosystems importance often only becomes apparent after major change has taken place. In the case of the gut microbiota, we may have to confront the daunting task of reconfiguring an ecosystem that we are just beginning to understand. Biodiverse ecosystems are characterized by complex networks of interactions; delete or add one node and the cascade of changes through the network of interactions can be difficult to anticipate. Predicting ecosystem changes from species reintroduction, such as wolves into Yellowstone National Park, is a challenge long faced by conservation biologists (63, 64) (Fig. 2A).

(A) Gray wolves were introduced into Yellowstone National Park in 1995 to control the swelling elk population (105). The rewilding of Yellowstone set off a trophic cascade that resulted in a decreasing elk population (thereby promoting new growth in aspens), an increase in berries available to bears, and stream morphology changes caused by increased woody plants (64). This provides an example of how wildlife management can be used to restore a more diverse and perhaps functional ecosystem, as well as how reintroduction of species into a habitat can lead to unanticipated changes to that ecosystem. (B) Rewilding of a C. difficileinfected microbiota by FMT results in largely predictable outcomes in host health, but the specifics of the resulting microbiota composition are difficult to predict. (C) Long-term strategies for managing the microbiota include precision approaches of adding defined cocktails of microbes, engineered bacterial species, and improving ecosystem habitat quality. For example, increasing dietary MACs encourages commensal growth and provides fermentation end products such as butyrate to the epithelium, which can help keep oxygen tensions lower in the gut and prevent the growth of facultative anaerobes with pathogenic potential (106).

Fecal microbiota transplantation (FMT) is an example of how ecosystem remodeling through multispecies rewilding can be applied to the gut microbiota. In this procedure, all of the bacterial species of a healthy human donors stool microbiota are introduced into a diseased recipient in an attempt to reconfigure a maladaptive ecosystem (Fig. 2B) (65). FMT has been highly effective in treating Clostridium difficile infection (CDI) refractory to conventional antibiotic-based treatment (66). Although this procedure cures CDI, the addition of hundreds of microbial species into an equally complex, although disrupted, ecosystem results in an unpredictable community that is composed of strains from the donor, recipient, and other sources (67, 68). CDI represents an extreme case of ecosystem disruption; therefore, the lack of precision in dictating the resulting community after ecosystem rewilding is clinically tolerable, as almost any resulting microbiota configuration lacking or minimizing C. difficile is preferred. However, FMTs are not an ideal long-term solution for the treatment of many diseases. In many cases, they are simply ineffective, and in others, the unintended consequences may include transmission of antibiotic-resistant microbes or other infectious agents and the transference of unwanted phenotypes from the donor (69). Gut microbiota rewilding through FMT has currently only been consistently successful for C. difficile cases. Similar to cases of animal reintroduction in macroecosystems, success as defined by the ability of these reintroduced species to thrive has been mixed (70).

Targeted rewilding through discrete changes in habitat quality or the introduction of specific species chosen based on known interactions may be a more predictable and successful approach to ecosystem management in a disrupted gut microbiota. Habitat quality is a key element of success in macroecosystem restoration and is also an important consideration in the gut (71). Ecosystems are made up of interacting species and their physicochemical environment. Factors that influence the suitability of the gut habitat, including temperature, pH, osmolality, redox status, water activity, and chemical and nutrient availability, will likely affect the success of microbiota reconfiguration efforts. Mice chronically infected with C. difficile can be effectively treated using a diet containing MACs. This simple change to habitat quality enabled the recovery of a robust indigenous community and reestablished important functions such as short-chain fatty acid (SCFA) production (72). Diet can also create a niche for a newly introduced microbial strain to colonize. For instance, feeding mice the seaweed polysaccharide porphyran allowed engraftment of a porphyran-utilizing Bacteroides strain (73). This example of engrafting a new species into a microbiota may provide a strategy that can be extended to help targeted rewilding (Fig. 2C).

An additional challenge to managing ecosystems is identifying the features within an ecosystem that are beneficial and thus worthy of conservation. One strategy used by ecologists is to assess the services provided by an ecosystem. Ecosystem services, popularized in the Millennium Ecosystem Assessment, enable value to be placed on different components of an ecosystem (74). For example, if a lake provides fresh drinking water and recreation (swimming, fishing), then pollution of that lake would put those services in jeopardy. Likewise, we can consider the ecosystem services supplied by the gut microbiota (75) (Fig. 3). However, determining whether a microbiota ecosystem service is beneficial is difficult enough in itself, and establishing whether this benefit is universal or specific to a subpopulation of people or even only one individual, a developmental period of life, or during disease or reproduction adds complexity. For example, extraction of calories was an important microbiota ecosystem service rendered in the preindustrialized world, but when eating modern, calorie-dense foods, this service becomes less important.

Identifying the benefits provided by the gut microbiome to human health is one way to determine when the ecosystem is functioning well. (A) List of benefits provided by the gut microbiota. This list is not intended to be comprehensive, and the categorization is only one of many possibilities, but it is presented as a potentially useful framework for conceptualizing how to value specific features of microbiota. (B) Current data suggest that, along with the shift in the composition of the industrialized microbiota, certain services may be lost or out of balance, resulting in suboptimal states of host physiology or disease. A more nuanced understanding of which services are beneficial and in what context will be enabled by longitudinal high-dimensional profiling of microbiome and host biology combined with long-term monitoring of health in humans.

Studying microbiota configurations in different contexts may reveal associations that are positive for human health. For example, work on the gut microbiota in individuals undergoing immunotherapy to treat cancer has shown associations between specific microbiota components and improved outcomes (76). Although many specifics remain to be determined, these findings are consistent with the ability of different microbiotas and their services, such as SCFA production, to alter host immune status and function. Unfortunately, such observational work is usually conducted on people living in industrialized countries and therefore is limited in the microbiota configurations and features that are queried.

If humans have developed a dependence upon microbiota services that have been lost during industrialization, then might reintroduction of these services be analogous to complementing a lost portion of human biology and provide broad benefit? Even if this is not the case, given the recent success of prophylactic antibiotics in low- and middle-income countries in improving health and reducing mortality in children, rewilding the microbiota after treatment using defined key strains may become a standard treatment to aid in ecosystem recovery (77). Should this be the case, then considerations of how to make reintroductions self-sustaining, especially in the face of spreading industrialization, will be important.

The goals of a managed microbiota should be to optimize ecosystem services to prevent disease and improve health and longevity. Optimization requires precise, targeted approaches that consider an individuals genotype, microbiome, or subcategory of disease. Given the large global health impact, strategies to protect the microbiome in all populations should be considered to maximize the palette of microbial and molecular tools available. Efforts are under way to archive the microbial diversity found in the gut of humans around the globe (35, 36). Whether these efforts will result in new therapeutics remains to be seen, but at the very least they provide a time capsule of microbial diversity in a rapidly industrializing world. Industrialization of the microbiome, and its accompanying loss or reduction of certain species, can occur on a time scale of months within an individual, creating some urgency for the banking of vulnerable species (78). An additional challenge is navigating the changing restrictions on the distribution of bacterial strains for research and therapeutic development while protecting the rights and recognizing the contribution of the people from which they came (79, 80).

Reshaping ingrained aspects of industrialized societies to moderate practices that have negative impacts on the microbiota will be a challenge but will be more practical than reversion to preindustrial practices (see Box: Sustainable ecosystem management approaches). Antibiotic use will remain an important aspect of industrial life; however, regulation in clinical and agricultural settings is needed to maintain efficacy and to protect the microbiome. Similarly, rationally engineered microbial cocktails or fermented foods could offer safe microbe exposure to compensate for sanitization. Government subsidies similar to those provided for certain crops could be justified to make MAC-rich and fermented foods cheaper and more widely available. Until food policy reflects the findings of biomedical research, short-term solutions, such as supplementing processed foods with MACs or probiotic bacteria, could provide a gradual progression toward health-optimizing food systems in industrialized countries.

Expanding cohort and interventional studies in humans from a wide representation of humans while simultaneously documenting microbiome and health changes is key for healthy, sustainable microbiota. Numerous associations have been made between the microbiota and human disease, but additional microbiome datasets from longitudinal, prospective observational and interventional studies of humans will provide insight into causal relationships. High-resolution measurements of host biology, including omics approaches and high-dimensional immune profiling, will be important to elucidate the specific lifestyle practices that lead to the most meaningful microbiome changes for human health (44, 81, 82). Animal models informed by human-derived data can be used to perform controlled studies with the goal of developing strategies to rebuild and maintain a healthy microbiota (83).

Some of the specific forces that are bad for Earth appear also to harm our microbiota. For example, animal meat production removes forest habitat for pasture and results in increased methane production. Excessive meat consumption has been coupled to trimethylamine-N-oxide (TMAO) production by the microbiota, and TMAO is a risk factor for cardiovascular events (84). It may be wise to approach climate and health and microbiota sustainability simultaneously to identify solutions that align Earth and human health (i.e., One World, One Health) (85). Given that environmentally sustainable agricultural practices are compatible with producing food generally recognized to promote health, solutions for the planet and human health may be compatible (86). As Earths microbes adapt to our changing environment, we can expect our bodys ecosystem to reflect our external environment in ways that are difficult to anticipate. Determining microbial or molecular equivalents of rewilding will require a much better understanding of community dynamics and hostmicrobiota interactions than we presently have. Continually monitoring and managing a healthy internal ecosystem may be an effective strategy to combat and prevent the litany of chronic diseases that are currently spreading with industrialization.

As we continue to learn of the multitude of benefits afforded by our microbial symbionts, developing alternative strategies to manage microbial ecosystems will enable us to promote short- and long-term public health priorities simultaneously (87). Listed here are a few examples of successes in using beneficial microbes to manage microbial ecosystems.

Sterility in skin-injury repair has been viewed as an important factor in effective wound healing. However, maintaining a sterile wound-healing environment is a difficult prospect considering the exposure of most wounds to the environment (88). Recent evidence suggests that populating wounds with commensal microbes can reduce infections after surgery and minimize the need for antibiotic treatment (89). Similar strategies are also being tested in treating skin conditions including atopic dermatitis (clinical trial NCT03018275) and acute wounds (90).

Health careassociated infections are pervasive in both high- and low-income countries and are a leading cause of death in the United States (91). Germicidal treatments of hospital surfaces are not completely effective, leaving behind dangerous pathogens, some of which can inhabit surfaces for months and also lead to increasing antibiotic resistance. The use of probiotic-containing cleaners can be an effective, alternative method to decontaminate hospital surfaces that does not select for antibiotic-resistant strains (92).

Concerns over increasing antibiotic resistance, consumption of antibiotic-laden meat, and antibiotic-induced reduction of natural resistance to pathogens have led to the exploration of alternatives to antibiotics in livestock. Probiotic use in chickens has resulted in better growth rates, reductions in pathogen load and antibiotic resistance genes, and improved egg quality (93, 94). Probiotics have also been used to prevent infections and improve milk production in dairy cows and to aid growth in beef cattle (95). Use of probiotics is also beneficial in aquaculture, improving water quality, resistance to pathogens, and growth (96).

There is growing evidence that the use of beneficial bacteria is a promising path forward for managing pathogenic microbes in humans (97). Probiotics can reduce the duration and severity of infectious diarrhea and may be an effective alternative to antibiotics in the treatment and prevention of bacterial vaginosis (98, 99). A synbiotic mixture of Lactobacillus plantarum and fructo-oligosaccharides reduced the incidence of sepsis and lowered rates of respiratory tract infection in a cohort of infants from rural India (100). The use of bacteriophage to control pathogens, especially those that are resistant to multiple antibiotics, is another emerging alternative with recent success (101).

Antibiotics are commonly used in cancer treatment to minimize the risk of infection in a patient population with a disrupted immune system. However, in animal models, antibiotic treatment can alter the microbiota in ways that reduce treatment efficacy (102, 103). In fact, specific manipulation of the microbiota improved immunotherapy-based tumor control in a mouse model of melanoma (102, 103). Optimization of the microbiota to optimize immune status, whether augmenting immunotherapy or enabling bone marrow transplantation, will likely be integral to the future treatment of diseases such as cancer.

Given newly acquired data about the importance of early microbiota assembly in the health of the infant, a rethinking of medicalized birth is warranted. A recent pilot study showed that infants delivered by C-section who were seeded with their mothers vaginal microbes developed microbiota more closely resembling those of vaginally delivered infants (104). Future studies are required to determine whether vaginal seeding after C-section delivery provides any lifelong health benefit to the infant.

Acknowledgments: We thank members of the Sonnenburg lab and collaborators for helpful discussions. Funding: This work was supported by the NIH (R01-DK085025 and DP1-AT00989201). J.L.S. is a Chan Zuckerberg Biohub Investigator. Competing interests: The authors declare no conflicts of interest.

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