Read More at Fight Aging! Within a species, variations in the operation of metabolism correlate with later life health and life span. Insulin metabolism is one of the more prominent and well studied examples. Much of this may stem from the lifestyle choices that epidemiology shows explain the majority of the variation in human life expectancy. Become sedentary or overweight and this pushes metabolism into a less optimal, more harmful state. The consequences to health and risk of mortality accrue over a long period of time, but are no less real for it. The study of aging has long been linked with the study of metabolism, as early theories pointed to the rate of metabolism and by-products of metabolism as drivers of aging processes. The earliest recognized interventions that caused life span extension in model organisms targeted nutritional and metabolic…
Chromatin Structure in Cell Aging and Senescence
Read More at Fight Aging! The constantly changing structure of nuclear DNA, packaged into chromatin, determines which genes are accessible to the machinery of gene expression, which determines protein production, which determines cell behavior and state. Chromatin structure and all of the determinants of that structure, including epigenetic marks such as DNA methylation, change as a cell ages towards the Hayflick limit and cellular senescence, and change in aged tissues versus young tissues. Given the advent of epigenetic reprogramming as a potential strategy for rejuvenation, questions regarding the ways in which epigenetics determines cell function in cellular senescence and aging become more pressing. Comprehending the role of molecular processes such as DNA damage repair, telomere shortening, nuclear and chromatin changes along with epigenetic alterations which drive aging as well as aging related diseases may hold a key to the “elixir…
The Idea that Epigenetic Clocks Will Point to Causes of Aging
Read More at Fight Aging! This popular science article on the development and present use of epigenetic clocks mentions the view that the clocks will point the way to a better understanding of the causes of aging. I’m dubious that use of the clocks represents a better way forward to that goal than the approach of implementing the various rejuvenation therapies outlined in the SENS proposals. A potential rejuvenation therapy that affects just one potential root cause of aging in isolation will tell us a lot about the importance and validity of that cause; researchers are learning a great deal from the ability to selectively destroy senescent cells, for example. Even good correlations between epigenetic states and aging will, unfortunately, take a long time to pick apart into knowledge of which mechanisms influence those epigenetic states, and to what degree.…
Connections Between Epigenetic Aging and Nuclear DNA Damage
Read More at Fight Aging! Today’s open access paper reviews what is known of the connections between epigenetic aging and the nuclear DNA damage that occurs across a lifetime, and particularly in later life. Some of this DNA damage is more evidently connected with the epigenetic regulation that determines the packaging and structure of nuclear DNA, such as the activity of transposable elements, restrained in youth, but unleashed to copy themselves in later life, damaging genes as they do so. It is important to note that the relationship of cause and consequence between nuclear DNA damage and epigenetic change is likely a two-way street, particularly given the comparatively recent discovery that repeated double strand break repair causes epigenetic alterations characteristic of aging. While nuclear DNA damage raises the risk of cancer, such as via damage to cancer suppression genes, it…
MItochondrial Epigenetics in Aging and Cancer
Read More at Fight Aging! Mitochondria, the power plants of the cell, are the descendants of ancient symbiotic bacteria, and still carry a remnant circular genome, separately from the DNA of the cell nucleus. Some forms of mutational damage to mitochondrial DNA, and the downstream consequences of that damage, are thought to be an important contributing cause of degenerative aging, but what about epigenetic changes? Epigenetic aging in nuclear DNA is a hot topic at the moment, so it is inevitable that attention would turn to the epigenetics of the much smaller mitochondrial genome. Inflammation is a defining factor in disease progression; epigenetic modifications of this first line of defence pathway can affect many physiological and pathological conditions, like aging and tumorigenesis. Inflammageing, one of the hallmarks of aging, represents a chronic, low key but a persistent inflammatory state. Oxidative…
More Data on the Effects of Aging on the Gut Microbiome
Read More at Fight Aging! The gut microbiome changes with age, a shifting of microbial populations that increases chronic inflammation and reduces the production of beneficial metabolites. These changes may be largely due to the age-related decline of the immune system, responsible for removing unwanted microbes, but significant changes occur early enough in life, in the mid-30s, for there to be other factors involved. Researchers are actively engaged in mapping the differences between an old microbiome and a young microbiome, work that will likely lend support to various approaches to therapy intended to rejuvenate the gut microbiome, forcing its balance of microbes towards a more youthful configuration. Probiotics are an obvious strategy, but much more data is needed to validate the specifics of such an approach, and it is far from clear that presently available probiotics, even in large amounts,…
Fight Aging! Newsletter, August 22nd 2022
Read More at Fight Aging! Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out more: https://www.fightaging.org/services/ Contents A Small Trial of NMN Supplementation Shows Improved Muscle Function Sepsis and Immunosenescence Combining BCL-2 Family Inhibitors May Yield More Effective Senolytic Therapies The Path to the Clinic for First Generation Senolytic Therapies A Reduction in the Time Spent in Poor Health at the End of Life, Despite Increased…
Why Incontinence Is Not a Normal Part of Aging
Read More at Sixty and Me Have you noticed how many ads on television promote the use of products for bladder control problems? And do you realize that nearly all of these ads are directed at women, even though many men experience bladder leakage, too? While I’m grateful that these products exist, the ads often make me cringe. Typically, they portray bladder leakage (incontinence) as a normal and unavoidable part of becoming an older woman. This is far from the truth. It is true that there are some forms of incontinence that are irreversible. However, many types of bladder control problems can improve or be corrected with proper treatment. Today, let’s look at the three most common types of bladder incontinence and possible treatments. Note that some people experience a combination of these conditions. Stress Incontinence Bladder leakage occurs when…
Epigenetic Aging Slows During Hiberation in a Common Bat Species
Read More at Fight Aging! This open access paper on epigenetic age and hibernation in bats makes an interesting companion piece to similar research into marmots from earlier in the year. It seems that hibernation may slow epigenetic aging in a range of species, though it may not be enough to explain differences in life span between all similar hibernating and non-hibernating species. Nonetheless, researchers have for some years shown interest in the biochemistry of hibernation in the context of aging. It remains to be seen what there is to learn here, and whether it can form the basis for therapies or enhancements in human medicine. Comparative analyses of bats indicate that hibernation is associated with increased longevity among species. However, it is not yet known if hibernation affects biological ageing of individuals. Here, we use DNA methylation (DNAm) as…
Towards the Widespread Use of Gerotherapeutic Drugs to Slow Aging
Read More at Fight Aging! Many compounds, small molecules, plant extracts, and so forth, have been found to modestly slow aging in mice. Given accumulating evidence from animal studies and human clinical trials, and that a sizable fraction of these compounds are already approved by regulators for other uses, or otherwise readily available, it is inevitably the case that physicians and the population at large will begin make use of these treatments in increasing numbers. This will happen, sometimes ahead of the science, sometimes behind it, sometimes to little benefit to patients, sometimes with enough of a benefit to matter. Navigating the options will become a great deal harder than it was, as we transition from an era in which little to nothing could be done to change the pace of aging, to one in which there are many options,…
Upcoming Events in Healthy Aging
Read More at Massachusetts Healthy Aging Collaborative The Massachusetts Healthy Aging Collaborative encourages stakeholders and communities involved in the age- and dementia friendly movement to check out the following upcoming events: Reimagining Intergenerational Housing Webinar (Aug. 23, 2:00 pm) Join Generations United and Nesterly for a webinar on August 23, 2022, at 2:00 p.m. EDT exploring the emerging continuum of intergenerational living approaches, including home sharing, Grandfamily housing, and others; and how communities and organizations can help advance them. Presenters will include Donna Butts of Generations United and Noelle Marcus of Nesterly. Registration is available here. Meeting the Needs of Diverse Family Caregiver Overview Training (Sept. 21, 1:00 pm) Caring for Those Who Care: Meeting the Needs of Diverse Family Caregivers is a training curriculum created by the Diverse Elders Coalition. This 90-minute Diverse Family Caregivers Overview training is designed for healthcare, social service…
Using Public Support to Lobby for Greater Public Funding of Aging Research
Read More at Fight Aging! I don’t pay a great deal of attention to the political lobbying efforts that take place in the community of supporters of aging research, as governmental funding is usually the last to the table, arriving long after the hard work of opening up a new field is done. There are a number of lobbying groups actively working in the US political system, and some single-issue political parties in Europe performing an analogous function. The material here is an example of the work taking place amongst those who lobby, the Alliance for Longevity Initiatives in this case. It is the business of persuading politicians that it is in their short-term interest to divert more funding into useful programs, while hoping that said funding doesn’t just get funneled into irrelevant and wasted efforts set up by the…
Discussing the State of the TAME Clinical Trial, Metformin to Slow Aging
Read More at Fight Aging! The TAME clinical trial, still not started, intends to assess the ability of metformin to marginally slow aging in humans. Back at the start of this initiative, it required a long process of negotiation on the part of the trial organizers with the FDA to produce an endpoint that was agreed upon to sufficiently represent aging. To my mind, the TAME trial initiative has already achieved what needs to be achieved: to get the FDA to agree that there is a way to run trials to treat aging. One doesn’t actually need to run the trial, and there is in fact little point in running the trial. Metformin is almost certainly a marginal treatment, and attention should be directed instead towards senolytics and other approaches that have much, much better animal data to support their…
Fight Aging! Newsletter, August 15th 2022
Read More at Fight Aging! Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out more: https://www.fightaging.org/services/ Contents A Short Commentary on Why We Advocate for the Treatment of Aging The Anti-Longevity Rhetoric that Characterizes Much of Aging Research Cellular Senesence, a Key Target in the Treatment of Aging Epigenetic Clocks Do Not Strongly Reflect Inflammatory Status? Towards Lasting Engineering of the Gut Microbiome Mechanisms Linking Red…
Inflammation and Cellular Senescence in the Aging Lung
Read More at Fight Aging! Here, researchers discuss what is known of the role of senescent cells, and the chronic inflammation that they create, in the aging of the lung. The first human trials of senolytic therapies to selectively destroy senescent cells were aimed at reversal of idiopathic pulmonary fibrosis. There is a good evidence for the growing presence of senescent cells to disrupt tissue maintenance and produce fibrosis as a result, the deposition of excessive, scar-like collagen structures that harm tissue function. There is a little that can be done to reverse fibrotic disease in the clinic, but animal studies showing improvement following clearance of senescent cells have given some hope for progress on this front. Cellular senescence, a coordinated cellular response to stress characterized by permanent cell cycle exit and the development of an elaborate secretory profile, is…
The Inflammatory Burden of Infection Accelerates Hematopoietic Aging
Read More at Fight Aging! Researchers here provide evidence for the inflammatory burden of infection to accelerate the aging of the hematopoietic system responsible for generating blood and immune cells. A greater exposure to infectious disease throughout life may be causing presently irreversible damage in the stem cell populations that produce the immune system. It is already known that restoration of these stem cell populations is an important target for the rejuvenation of the aged immune system, along with regeneration of the thymus and clearance of misconfigured and damaged populations of immune cells. It is unclear as to which of the many potential approaches to rejuvenation of hematopoietic stem cells will first succeed to a useful degree, but it seems likely that some form of cell therapy will be needed, an outright replacement of worn, damaged, and missing cells with…
Cellular Senesence, a Key Target in the Treatment of Aging
Read More at Fight Aging! Scores of animal studies provide compelling evidence for cellular senescence to contribute meaningfully to many age-related conditions, and yet more such studies demonstrate rapid and sizable rejuvenation via targeted removal of senescent cells in old animals using varieties of senolytic therapy. Senescent cells are created constantly in the body, the result of cells reaching the Hayflick limit on replication, tissue injury, or encountering cellular damage or toxicity. When an individual is young, these newly senescent cells are near all removed by a combination of programmed cell death and the actions of the immune system. Later in life, this balance between creation and destruction shifts, however, particularly because the immune system becomes less capable. As a result senescent cells begin to accumulate in tissues throughout the body. While the absolute numbers of senescence cells do not…
Klotho in the Pathology of Aging
Read More at Fight Aging! Klotho is a longevity-associated protein; more of it slows aging, less of it accelerates aging, at least in animal studies. While researchers have spent considerable effort investigating the effects of klotho on the brain, as it improves cognitive function, it seems likely that its effects arise via improved kidney function in old age. Loss of kidney function, and thus clearance of metabolic toxins and waste from the bloodstream, is harmful to tissues throughout the body. Manipulation of klotho may be a good way to assess just how much harm is generated by the age-related decline of the kidneys. The subject of this review is Klotho (kl), which is an antiaging gene, and the corresponding protein α-Klotho (henceforth denoted Klotho or KL). The gene was first identified in mice in 1997. Deficiency of the protein results…
The Anti-Longevity Rhetoric that Characterizes Much of Aging Research
Read More at Fight Aging! Sizable contingents in the aging research community and longevity industry like to assure us that greater human longevity is not in fact the goal of the growing level of investment in research and development of means to treat aging, or even desirable for that matter. It is a strange phenomenon. Cynically, one might suspect that those working on approaches based on cellular stress response upregulation, mimicking calorie restriction, that cannot in fact do much to extend life in longer-lived species such as our own, and will at best incrementally improve late-life health, are trying to make their work look better to the groups that funded it. Regardless of motivation, I think that propagating this sort of viewpoint is harmful to the future of the field. While it might be harder of late to make this…
SENS Research Foundation’s Ending Aging Forum, September 2022
Read More at Fight Aging! The SENS Research Foundation is hosting an online presentation of their work next month, a virtual Ending Aging Forum. If you are interested in the projects presently underway at the Foundation, and in allied labs, then mark your calendars. While the SENS view of aging as a process of damage accumulation, accompanied by a set of specific approaches to be taken to produce rejuvenation, has diffused somewhat into the broader longevity industry, that industry remains largely working on metabolic manipulation to slightly slow aging, not actual repair of damage. There is still a role for organizations focused on the SENS approach to aging and rejuvenation, accelerating the path towards meaningful rejuvenation therapies. Come spend a wonderful and thought provoking time with the team at SENS Research Foundation. This virtual event is your opportunity to hear…
A Short Commentary on Why We Advocate for the Treatment of Aging
Read More at Fight Aging! Recently, I had the occasion to make one of my very infrequent trips to the emergency room. As always the case to date, I get to walk out afterwards, after a very long period of hurry up and wait. Not everyone is so fortunate. One of the things one tends to find in emergency rooms is old people. So many more of life’s slings and arrows become an emergency when one is frail, and old people are increasingly frail. Fall over? Emergency room. Sudden infection? Emergency room. And so on and so forth. Nurses and doctors are inordinately overworked, and there is a long backstory to this state of affairs in which the American Medical Association, generations of regulators, and hospital owners all play the villain in turn. Emergency rooms are a great place to…
Interviews on Aspects of Aging with Judith Campisi and Dena Dubal
Read More at Fight Aging! Today I’ll point out a pair of interviews with researchers Judith Campisi and Dena Dubal, in which they discuss quite different aspects of aging. Campisi’s research has a heavy focus on cellular senescence in aging. Cells become senescent constantly in the body, most because they hit the Hayflick limit on replication imposed upon the somatic cells that are the overwhelming majority of cells in our tissues. Cells can also become senescent because of damage, or encouraged into senescence by the signaling of other, nearby senescent cells. Once senescent, cells are normally quickly removed by the immune system or programmed cell death mechanisms, but the balance between creation and destruction is disrupted with age, allowing the number of senescent cells to grow. These cells secrete a potent mix of signals that produce chronic inflammation and disruption…
Fight Aging! Newsletter, August 8th 2022
Read More at Fight Aging! Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out more: https://www.fightaging.org/services/ Contents Changes in the Behavior of Lipid Rafts in Aging Aging and the Severity of Inflammatory Infectious Disease Such as SARS-CoV-2 Are Pharmacological Approaches to Slow Aging in Fact Promising? Interviews on Aspects of Aging with Judith Campisi and Dena Dubal A Modest Gain in Mouse Lifespan via Pharmacological Means…