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The Evolutionary Perspective
Category Archives: Human Longevity
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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UN spotlights digitization of audiovisual archives to preserve human history on World Day - UN News
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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Can we predict the future? Bill Gates says yes, in this one area - CNBC
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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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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Does the human lifespan have a limit? - Varsity Online
Posted: at 3:36 pm
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.
Posted: at 3:36 pm
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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Vulnerability of the industrialized microbiota - Science Magazine
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With his remarkable and seemingly infinite power, the Monitor is a fascinating character in the DC Comics universe. He made his first appearance in 1982 in New Teen Titans but is better known for his appearance in the Crisis on Infinite Earths limited series from 1985. He has sparked attention again since showing up in the CW Arrowverse, delivering dangerous goods and watching the heroes scramble to combat the new threats in their midst.
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The Monitor possesses incredible cosmic abilities but they are never formally defined or explained in his storylines. Nonetheless, DC fans are shown a wide variety of Monitor's impressive powers over the course of his appearances in comics and on TV.
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The Monitor is not exactly immortal--after all, it becomes apparent that he can be killed. He does, however, possess amazing longevity. The Monitor spent billions of years watching over the multiverse prior to the events of Crisis, indicating his ancient status. He didn't age or deteriorate noticeably despite the passage of eons and never sustained injuries substantial enough to cause his downfall. The Monitor is essentially unlimited in ability, so it's really not surprising that he has been able to live such a long life. The actual extent of his longevity, though, is extraordinary.
The character of the Monitor is intricately linked with the concept of the multiverse in DC Comics. He was born shortly after the singular universe split into multiple and he later took on the role of overseer for all the worlds made of positive matter. In order to effectively observe these worlds, it was necessary for him to jump from one to another. He also had to take a trip across the multiverse in order to recruit the most capable heroes and form a team that would be able to overcome the impending threat looming in the Arrowverse TV shows.
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After the Monitor was born on Oa's moon, he began to meditate. While in this state he used his innate power to gather as much information as he could about the universe. This act alone provided him with a massive amount of knowledge that would act as a foundation for his future decisions. Over the course of his incredibly long life, this knowledge naturally continued to grow through exposure to events across the multiverse. The Arrowverse has featured its fair share of brilliant characters, but few are likely to compare to the Monitor.
When it comes to moving throughout the multiverse, teleportation is the most practical method of travel. The Monitor is able to disappear and reappear as needed and takes the opportunity to use this power for dramatic effect. In the first issue of the Crisis series, he teleports into a room where his chosen heroes are gathered, a blinding flash of light announcing his arrival. He also appears able to transport others via teleportation, as seen in the Arrowverse's "Elseworlds" crossover event when he brought the Green Arrow from a building on Earth-1 to an isolated, starry space.
Teleportation isn't always necessary for moving from one place to another, and that's when the power of flight comes in handy. Some superheroes are defined by their ability to fly, being so closely associated with it that it overshadows many of their other powers. This is far from the case for the Monitor; his abilities are so tremendous and so varied that flight is not often seen from him and is easily forgotten. However, flight is still an impressive and notable ability to have and should not be overlooked, even in the case of a being as capable as the Monitor.
The Monitor has a level of awareness well beyond that of the average human. He often gives warnings to the heroes he encounters indicating that he has an idea of what will unfold in the near future, even if he isn't completely certain. He is more sensitive to what is going on in the present as well. During "Elseworlds", Cisco used his vibing abilities in an effort to quietly peek in on the Monitor. However, the Monitor became almost instantly aware of the hero's power use, looking back at Cisco and addressing him directly.
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Telekinesis is an extremely useful power when it comes to facing off with super-powered beings, allowing the user to inflict damage to their enemy without having to get too physically close. While the Monitor has an extensive arsenal of other powers as well, telekinesis is one that has benefited him greatly, though not always as an attack. When he first approaches John Deegan in the "Elseworlds" crossover event, the psychiatrist is understandably skeptical of him. The Monitor uses his telekinetic power to crush a car, effectively demonstrating his power and intimidating Deegan.
Finding the individuals he is looking for is no challenge for the Monitor. Whenever he has needed to contact someone, he has been able to simply teleport directly to their location, appearing in front of them regardless of where in the multiverse they are. This act suggests that he is able to sense where an individual is at any given time. He is also described as being able to sense his brother, the Anti-Monitor, a being that is his equal but existing in a universe made of anti-matter. His awareness of his brother's existence allowed him to track him and fight with him from his home moon.
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Living for billions of years is an amazing thing, but without the ability to hold strong in lengthy endeavors there's little point to having such an extended lifespan. Luckily for the Monitor, superhuman stamina is in his toolkit. Neither his body or his mind tire easily and he is able to push through challenges with strength and determination. Without his impressive stamina, he would not have been able to keep up the fight against the Anti-Monitor, a battle which raged on between them for millions of years before they knocked each other out.
Metron, an explorer of mysterious origin, once described the Monitor as a being capable of creating from thought. This description suggests that the Monitor has the ability to bring anything into existence and supports the notion that his power is practically unlimited. Compared to the most powerful of Earth-1's heroes, the Monitor is more or less a god. He used this power to save Pariah after his world was destroyed by the Anti-Monitor and likely used it to create some of the weapons he provided to various villainous characters across the multiverse.
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Posted: August 25, 2017 at 3:38 am
By Austin Lombard Special to In Motion
My cellphone. Its so much more than just a device.
I use it to call people. I use it to navigate in the car. I use it to look up recipes in the kitchen. I use it as my shopping list in the grocery store. I use it to read the news.
Smartphones like mine and electronics like the computer Im using to write this are so ubiquitous in modern lives that few question where they come from or where they go. Electronics are so essential to civilization that we take them for granted.
But the amount of resources that go into making these devices is staggering. Manufacturing a single computer and monitor requires at least 530 pounds of fossil fuels, 50 pounds of chemicals and 3,000 pounds of water. The U.S. Environmental Protection Agency also lists copper, silver, gold and palladium as just a few of the valuable metals contained in our electronics.
Even so, the cost of sourcing and manufacturing electronics cannot strictly be measured in mineral resources. All along the supply chain and manufacturing, human labor is required to make them possible. Over the last decade, the ethical implications of sourcing and manufacturing electronics has come into sharp scrutiny, particularly because of its contrast with the exorbitant wealth the industry brings to the engineers living in technology-driven economies in cities like Cupertino, Calif. and Bellevue, Wash.
Electronics dirty secret
In 2010, manufacturing giant Foxconn experienced a rash of suicides at its Shenzhen campuses in China, prompting the company to install nets around the manufacturing plant to prevent employees from taking their own lives. The New York Times reported that one 19-year-old victim there worked over three times the legal limit of overtime in the month before his death. In 2015, Reuters news agency reported that South Korean electronics company Samsung agreed to create an $86 million fund to compensate workers who contracted cancer working with hazardous materials at its manufacturing facilities.
Sourcing materials can come at a heavy human cost. Awareness of conflict or blood diamonds hit the U.S. mainstreams attention when Kanye West released his song Diamonds from Sierra Leone in 2005. The music video contrasted images of wealthy Europeans and himself wearing diamonds, with images of child slaves mining those diamonds under the watch of armed rebel guards.
What didnt gain as much attention, however, were other valuable metals with less shine: minerals like copper and cobalt. The United Nations Office on Drugs and Crimes 2011 report on Organized Crime and Instability in Central Africa cited those two minerals as a serious source of funding for organized crime in the Democratic Republic of the Congo. Most of us probably own less diamonds than Kanye, but we all have a cell phone.
News reports have prompted electronics industry leaders such as Intel and Apple to establish initiatives to audit their supply chains and manufacturing sites for human rights violations. While a step in the right direction, these measures are not a complete solution. Even Intels 2017 Conflict Minerals White Paper a corporate communication detailing its efforts to eliminate conflict minerals from its supply chain admits that Conflict-free sourcing is not fully resolved, even after a decade of diligence. To this day, manufacturing sites draw controversy. Yet, other electronics companies have not bothered to establish official missions to eliminate human rights abuses from supply chains and manufacturing processes.
Our problems with electronics, unfortunately, do not end at manufacturing. The most difficult problem of all lies in the disposal of obsolete or broken electronics, or e-waste. E-waste from printers, monitors, computers and phones contains high levels of toxins, such as lead, mercury and cadmium. Because these toxins can seep out of e-waste and contaminate water sources, it is illegal to send them to landfill in the United States. Because of this, all government agencies urge consumers to recycle used electronics. But thats the problem
The Basel Action Network and Massachusetts Institute of Technology worked in partnership to conduct a study: GPS devices were attached to discarded electronics and given to certified recyclers. In the Basel Action Networks press release, it was reported that about 40 percent of the deliveries were exported, mostly to China. Recycling operations in developing countries are typically carried out by people living in abject poverty, using practices that disregard the safety of the laborers and the environment because they are unaware of the dangers the materials pose.
Yuan Chun Li and Banci Lians book, E-waste: Management, Types, and Challenges, describes approximately 1.6 million tons of e-waste sent to the junkyard town of Guiyu annually. The air there is thick with lead fumes from de-soldering operations, plastics and flame retardant chemicals are burned in the open with no breathing protection, and runoff from gold reclamation makes water so acidic that merely touching it will burn your skin. Children are stillborn or born with defects at a high rate. Farming villages are transformed into toxic wastelands.
Sustainability key to success
So if recycling is a poor option, what can we do? Some of you might be familiar with the three Rs of sustainability: Reduce, Reuse, Recycle. These three Rs are listed in order of importance. We need to look at reducing the amount of electronic waste we generate. We can start to do this by taking care of our electronics and by repairing and upgrading devices. When a part breaks or becomes obsolete, we should replace only that part, rather than throwing the entire device away and buying a new one. IFixIt.com is a wiki-styled website with user-contributed repair guides, as well as staff teardowns and reviews that rate devices on the ease with which they can be repaired. New enterprises like Fairphone put human rights, repairability and device longevity first. The first stirrings of change are in the air, if you know where to look.
The ugly burden of our digital age is a complicated problem. Fully solving it requires electronics corporations to change the way they do business. Environmental regulations must be created and enforced to prevent unscrupulous dumping of toxic waste on the impoverished people of our world. Ultimately, laymans attitudes on electronics need to shift to sustainability, using a device until it cannot be repaired, rather than upgrading every time a new device comes out on the market.
For most of us these requirements may seem out of our hands. But by choosing products built for repairability and longevity, ordinary people can influence the market to produce sustainable products. As business strategist and sustainability expert Brian Moore states in his book, IT Sustainability for Business Advantage, one of the biggest factors in promoting sustainability within business is simply that it matters to stakeholders and consumers.
Only when consumers, shareholders, and voting citizens like us begin to refuse to ignore the blood and lead staining our hands, will business and government follow suit.
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Posted: at 3:38 am
A 125-year life expectancy for human beings? I have zero desire to stick around that long.
Ah, yes, you speak of a debate among scientists over human longevity. I read about it at Business Insider. Some scientists argue that the maximum age humans may live is 115 years, whereas others argue that 125 years is possible.
A hundred and twenty-five years of watching Republicans and Democrats going at it? The heck with that.
Living is rife with challenges, to be sure. But living a long life has its upsides. Wouldnt you want to visit your parents and other family members for a lot more years than most of us are able? Wouldnt you like to see them all at a Sunday dinner several more times than most human beings are able?
Maybe with your family. My family has taken years off of my life!
I see, but wouldnt it be awesome if some of our finest human beings could stick around longer? Don Rickles, one of the greatest entertainers ever, died this year at 91. How great would it be to keep him around for two more decades?
True, but if Rickles were to stick around longer, that means annoying celebrities would stick around, too, and keep yapping at us every time a Republican becomes president.
There are other upsides to a longer life. What if we could keep our greatest minds around longer? Where would the world be if Einstein had another 25 years to unlock the mysteries of the universe?
But what if he figured out ways to extend human life even further, which would require me and the wife to have to keep coming up with new things to bicker about? Who has that kind of energy?
The downsides are a fair point. As people live longer, they could overburden government programs, such as Social Security. Where would we get all the money to support them?
How about we especially extend the lives of the rich so we can take them to the cleaners?
And living is expensive. If you live to 125, how will you pay for your housing and food and everyday expenses?
Thank goodness McDonalds is always hiring, but I for one have no desire to flip burgers at the age of 125.
The costs of medical care are too high for millions now. I imagine that at 125 years of age, ones medical bills would be difficult to manage.
Look, as a middle-aged guy, who is already showing signs of fatigue, here is what I know about living. Life is largely made up of colds, bills, speeding tickets and people who let you down. These experiences are connected together by a series of mundane tasks.
Did anyone tell you how cheerful you can be? Go on.
Well, these drudgeries are occasionally interrupted by a wonderful meal, a really good laugh with friends or a romantic evening with a lovely woman. Then the mundane stuff starts all over again. Who wants 125 years of that?
A lot of people do. The human lifespan has improved significantly in the past few generations. Millions are living healthy lives beyond the age of 80 today, and, when they were younger, few of them expected to live that long. Why not live relatively good lives until 125?
Because then Id really worry about my slacker son.
Hes 35 years old and still living at home. If we drastically extend lifespans, my wife will have to tell him: Son, youre 100 years old! When are you going to move out of the basement and get a job?
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Living to 125 Too Much of a Good Thing? - Pike County News Watchman
Celularity, Inc., Accelerates Breakthrough Placental Discovery & Therapeutic Platform – Business Wire (press release)
Posted: August 22, 2017 at 11:30 pm
WARREN, N.J.--(BUSINESS WIRE)--Celularity, Inc., a newly formed biotechnology company, today announced its acceleration of cell and tissue regenerative therapies to address unmet medical needs in cancer and chronic and degenerative disease. Celularity completed their Series A financing with contributions from several biopharma companies, including Sorrento Therapeutics, United Therapeutics Corporation and Human Longevity, Inc., and entrepreneurial investors.
Celularity has been created through the contributions of extensive intellectual property, clinical-stage assets, basic and clinical research, and development expertise including:
Founded on the pioneering work of Robert Hariri, MD, PhD, in human placenta-derived cellular therapeutics and biomaterials, Celularitys ability to procure placental stem cells, engineer potential therapies, and deploy potential treatments, positions it to harness the potential of the human placenta and operate along the entire value chain.
Celularity was formed as a new biotechnology model designed to apply the necessary expertise to harness our placenta discovery platform across a range of unmet medical needs, said Celularity Founder and Chief Executive Officer, Robert J. Hariri, MD, PhD. With the support of our investors, we are assembling proven regenerative medicine technology and expertise with the goal of developing transformative therapies for fatal and intractable diseases. Dr. Hariri was previously chairman, chief scientific officer and chief executive officer of Celgene Cellular Therapeutics and founder of Anthrogenesis Corporation, which Celgene acquired in 2002. Dr. Hariri is also the co-founder of Human Longevity, Inc.
The formation of Celularity leverages seminal work in the discovery of novel biologically active cell populations in the human placenta with broad therapeutic potential. Celularity will draw upon these proprietary and scalable discoveries that derive from the post-partum human placenta an ethical and renewable source of usable biomaterials. Celularitys development program is focused on an allogeneic platform, leveraging clinically accessible, immune-tolerant cells and biomaterials from a diverse population of informed-consent donors.
Andrew von Eschenbach, MD, among the founding members of the Celularity Board of Directors and former United States Food and Drug Administration (FDA) Commissioner and Director of the National Cancer Institute said, The pioneering work of Celularity founder Bob Hariri has unleashed the unique properties of placental derived stem cells which have renewed hope for creating safe and effective therapies for the most challenging degenerative diseases." Dr. von Eschenbach added " Celularity with its focus on accelerating innovation in regenerative medicine can become the leading catalyst for cell therapy to address many of the world's unmet medical needs."
*Interfyl is a registered trademark of Alliqua BioMedical, Inc.
Dr. Henry Ji, President and CEO of Sorrento Therapeutics, said, We are very excited to participate in the creation of Celularity together with Dr. Hariri and his scientific team as well as global leading biopharmaceutical companies, such as Celgene, Human Longevity Inc., and United Therapeutics. The potential for regenerative therapies in treating a wide array of chronic degenerative conditions is well known. We see important synergies for the oncology field and the potential to enhance our fight against malignant cancers. Celularitys technologies, assets, and resources will help advance selected Sorrento cellular therapy programs and potentially transform autologous cellular therapies into affordable and accessible allogeneic cell therapies.
About Celularity, Inc.
Celularity, headquartered in Warren, New Jersey, is a biotechnology company with proprietary, leading-edge technology and Intellectual Property to harness the power of the placenta. Their medicine asset portfolio consists of more than 200 issued or pending patents as well as pre-clinical and clinical assets including CAR constructs for allogeneic CAR-T/NK products, licenses of 100+ immunotherapy assets, and commercial stage biosourcing and functional regeneration businesses. For more information, please visit http://www.celularity.com. Follow Celularity on Social Media:@Celularity.
About United Therapeutics
United Therapeutics Corporation is a biotechnology company focused on the development and commercialization of innovative products to address the unmet medical needs of patients with chronic and life-threatening conditions.
About Sorrento Therapeutics
Sorrento is an antibody-centric, clinical stage biopharmaceutical company developing new treatments for immuno-oncology, inflammation and autoimmune diseases. Sorrento's lead product candidates include immunotherapies focused on the treatment of both solid tumors and hematological malignancies, as well as late stage pain products. For more information, please visit http://sorrentotherapeutics.com
About Human Longevity, Inc.
Human Longevity, Inc. (HLI) is the genomics-based, health intelligence company creating the worlds largest and most comprehensive database of whole genome, phenotype and clinical data. HLI is developing and applying large scale computing and machine learning to make novel discoveries to revolutionize health. In addition to the HLIQ Whole Genome and HLIQ Oncology, HLIs business also includes the HLI Health Nucleus, a genomic powered clinical research center which uses whole genome sequence analysis, advanced clinical imaging and innovative machine learning, along with curated personal health information, to deliver the most complete picture of individual health. For more information, please visit http://www.humanlongevity.com or http://www.healthnucleus.com