Calorie Restriction versus Cancer, Viewed in Terms of Growth Signaling
The practice of calorie restriction, eating fewer calories while still obtaining sufficient micronutrients, is well demonstrated to reduce cancer risk in animal models, and also appears to improve outcomes in the case of an established cancer. This is similarly the case for practices such as intermittent fasting or fasting mimicking diets, the latter having undergone trials as an adjuvant therapy in human cancer patients. Researchers here review this topic through the lens of nutrient sensing and growth signaling in the body, such as the well studied pathways involving growth hormone and IGF-1. More growth means more DNA d...
Source: Fight Aging! - October 18, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

A MicroRNA Signature of Cognitive Decline
An enormous amount of data can be derived from analysis of the cells and molecules found in a blood sample. Researchers will be kept busy for decades yet, ever more fficiently gathering and mining this data, in search of ways to assess the progression of aging and specific age-related diseases. The work here is interesting for finding a correlation between the abundance of a small number of microRNA molecules and age-related cognitive decline. Many microRNAs are promiscuously involved in the regulation of important cellular pathways, altering the expression levels of proteins that are themselves important the regulation of...
Source: Fight Aging! - October 18, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, October 18th 2021
In this study, we therefore analysed the influence of lithium treatment on lifespan and parameters of health during ageing in mice. To determine the concentration of lithium suitable to be administered in a longitudinal ageing study, we first tested the effects of lithium chloride (LiCl) in doses from 0.01 to 2.79 g LiCl per kg chow. C57Bl/6J mice fed with 1.05-2.79 g/kg LiCL in the diet showed lithium plasma levels between 0.4 and 0.8 mM/l. While plasma levels to 0.4 and 0.8 mM/l are well tolerated by human patients, at doses above 1.44 g LiCl/kg, we observed an obvious dose-dependent polydipsia combined with a dis...
Source: Fight Aging! - October 17, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Towards a Small Molecule Approach to Thymic Regeneration
The thymus is vital to a sustained and functional immune system. Thymocytes generated in the bone marrow migrate to the thymus, where a complex process of maturation and selection takes place, turning the thymocytes into T cells of the adaptive immune system. T cells must be capable of recognizing and reacting to pathogens and cancerous cells, without mistakenly attacking any of the normal systems of the body and its diverse cell population. That risk of self-immunity is the price of an adaptive immune system. The wide range of autoimmune conditions observed in the human population demonstrates that evolution does not prod...
Source: Fight Aging! - October 15, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Trial of the Senolytic Fisetin as a Treatment for Older SARS-CoV-2 Patients
We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. Link: https://doi.org/10.1111/jgs.17416 (Source: Fight Aging!)
Source: Fight Aging! - October 15, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

An Example of Senomorphic Drug Discovery
Senescent cell accumulation is a feature of aging, a growing imbalance between the rate of creation and rate of destruction. Senescent cells perform a number of useful tasks in the short-term, but when present for the long-term, their inflammatory secretions disrupt tissue function and contribute meaningfully to the onset and progression of age-related disease. A great many research groups are working towards the basis for therapies that can selectively destroy senescent cells (senolytics). Others are working on ways to prevent cells from becoming senescent, or suppress the worst of the bad behavior of existing senescent c...
Source: Fight Aging! - October 15, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Supplement Industry is a Corrosive Presence, Lacking in Integrity
Senolytic therapies selectively destroy senescent cells, an important cause of inflammation and tissue dysfunction in older individuals. Removal of senescent cells via pharmacological means produces impressive demonstrations of rejuvenation in old mice, reversing the progression of many different age-related conditions. An intermittent or one-time high dose of fisetin has been tested as a senolytic in mice, and showed surprisingly good results. Why surprising? Because the similar compound quercetin does not appear to be meaningfully senolytic on its own. Quercetin improves the ability of the senolytic dasatinib to kill sen...
Source: Fight Aging! - October 14, 2021 Category: Research Authors: Reason Tags: Healthy Life Extension Community Source Type: blogs

The Rejuvenome Project Announces Collaboration with the Buck Institute
I recently noted the Astera Institute's Rejuvenome project. The work will be conducted in collaboration with the Buck Institute. It is a sizable proposal, to conduct large and rigorous mouse studies with the ultimate goal of testing combined interventions, a necessary activity that the research community and industry alike largely fail to carry out. This is a big problem in the field of aging, as aging is the outcome of a range of distinct processes of damage accumulation. Sizable degrees of rejuvenation or slowing of aging can in the long run only emerge from combinations of approaches, repairing or working around multipl...
Source: Fight Aging! - October 14, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Senescent Cells Hinder Fracture Repair, Rather than Helping as Might Be Expected
Regeneration might be thought of as a complex and highly coordinated interaction between stem cells, somatic cells, and senescent cells. Some small fraction of cells in the injured tissue become senescent, cease replication, and secrete pro-growth, pro-inflammatory factors. They are then removed by the immune system once their task is done, to prevent long-term disruption of tissue function by those same secretions. The problem of senescent cells in aging is entirely that this signaling for growth and inflammation, beneficial in the short term, becomes very harmful and disruptive to normal tissue function when present for ...
Source: Fight Aging! - October 14, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Gene Therapies Make Compensatory Metabolic Adjustment More Precise, But That Still Isn't Damage Repair
Given a suitable delivery system, one that localizes to the desired target tissues to a far greater degree than to all other undesirable off-target tissues, the big advantage of a gene therapy is it precisely achieves the manipulation desired. It dials up or dials down expression for selected genes, alters the amount of proteins produced from those genes, and thereby changes cell behavior as a consequence - and that is all it does. One doesn't have the endless concern about off-target effects that characterize small molecule drug development. There are, of course, different challenges. Setting aside some adventurous...
Source: Fight Aging! - October 13, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Lithium Produces Mildly Positive Effects on Healthspan in Mice
In this study, we therefore analysed the influence of lithium treatment on lifespan and parameters of health during ageing in mice. To determine the concentration of lithium suitable to be administered in a longitudinal ageing study, we first tested the effects of lithium chloride (LiCl) in doses from 0.01 to 2.79 g LiCl per kg chow. C57Bl/6J mice fed with 1.05-2.79 g/kg LiCL in the diet showed lithium plasma levels between 0.4 and 0.8 mM/l. While plasma levels to 0.4 and 0.8 mM/l are well tolerated by human patients, at doses above 1.44 g LiCl/kg, we observed an obvious dose-dependent polydipsia combined with a dis...
Source: Fight Aging! - October 13, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Engineered B Cells as an Approach to Cancer Therapy
Engineered T cells are the dominant form of cell therapy for cancer at the present time, an approach that has achieved considerable success, and remains actively under further development. T cells can attack cancer cells directly, given the right tools to recognize those cells and overcome the various immunosuppressive mechanisms deployed by cancerous tissue. There are other approaches to rousing the immune system to action, however, such as focusing on B cells. B cells carry out a variety of roles that are important in the coordination of the immune response, in providing targets for other cells to attack, and rousing tho...
Source: Fight Aging! - October 13, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Early Years of Mitochondrial Transplantation as a Therapeutic Strategy
Mitochondria are the power plants of the cell, generating the chemical energy store molecule adenosine triphosphate (ATP). Throughout the body, mitochondrial function declines with age, leading to corresponding declines in tissue and organ function. This universal malaise appears to be a downstream consequence of the underlying causes of aging. Those causes in some way lead to changes in gene expression that alter mitochondrial dynamics in ways that reduce the efficacy of the quality control mechanism of mitophagy. When not regularly destroyed, worn and dysfunctional mitochondria accumulate, and ATP production suffers. ...
Source: Fight Aging! - October 12, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Greater Expression of Mitochondrial Base Excision Repair Enzymes in Longer-Lived Mammalian Species
The hundreds of mitochondria present in every cell are critical to cell function. As the descendants of ancient symbiotic bacteria, mitochondria have their own remnant DNA, separate from the chromosomal genomic DNA present in the cell nucleus. Both sorts of DNA suffer similar forms of mutational damage and are attended by broadly similar repair mechanisms, but nuclear DNA is by far the better protected and maintained of the two. Some forms of mitochondrial DNA mutation, particularly the deletion of genes important to the electron transport chain, are thought to confer both dysfunction and competitive advantages to mitochon...
Source: Fight Aging! - October 12, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Exploring Mechanisms by Which Exercise Slows Cancer Progression
Cancer patients who exercise tend to do better than those who do not. While one cannot escape an established cancer via physical activity, one can modestly slow it down, it appears. Researchers here explore some of the mechanisms by which exercise can achieve this goal, focusing on muscle tissue signaling that both slows cancer cell growth and provokes greater immune system activity. The usual path forward for this sort of research, given a large enough effect size to be interesting, is to try to find a way to deliver additional signal proteins as a form of treatment. This might be achieved directly using recombinant prote...
Source: Fight Aging! - October 12, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Arguing for a Central Role of Cellular Senescence in the Age-Related Susceptibility to Inflammatory Conditions
Inflammation is a necessary part of the immune response to injury and infection, required in order to defend and rebuild. Normally, inflammation is a cycle of signaling that changes cell behaviors, response followed by resolution. When resolution fails, serious consequences can result. Conditions such as sepsis and severe COVID-19 cases are examples of a runaway inflammatory response leading to a high mortality. Both of these examples are age-related, in the sense that old people are far more susceptible to undergoing such a breakdown of the normal inflammatory feedback loops. The age-related dysfunction of the immune syst...
Source: Fight Aging! - October 11, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Earlier Hypertension Correlates with Smaller Later Brain Volume and Raised Risk of Dementia
The increased blood pressure of hypertension causes structural damage to delicate tissues throughout the body, particularly in the brain. Beyond the matter of an increased pace of rupture of capillaries, killing tiny volumes of brain tissue, the blood-brain barrier is disrupted by pressure damage, allowing unwanted molecules and cells into the brain to provoke chronic inflammation and disruption of function. Blood pressure is so influential on health that lowering blood pressure via antihypertensive medication, an approach that does not in any way address the underlying causes of the problem, produces a reduction in mortal...
Source: Fight Aging! - October 11, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Extra Thymi and Lesser Thymic Involution with Age in Long-Lived Naked Mole-Rats
Naked mole-rats show little decline of function until late life, are highly resistant to cancer, and live nine times longer than similarly sized rodent species. An important aspect of immune system aging in mammals is the atrophy of the thymus. Thymocytes created in the bone marrow migrate to the thymus where they mature into T cells of the adaptive immune system. As active thymic tissue is replaced with fat, in the process of thymic involution, this supply of T cells declines. Absent reinforcements, the T cell population of the body becomes ever more damaged, malfunctioning, exhausted, and senescent. Researchers here show...
Source: Fight Aging! - October 11, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, October 11th 2021
In conclusion, this study examined how age and the process of aging are associated with changes in the microbiome of the small intestine, using validated sampling and processing techniques. The most significant differences are higher relative abundance of the phylum Proteobacteria and decreased relative abundance of Bacteroidetes in older subjects when compared to the youngest group. The higher relative abundance of Proteobacteria appeared to affect other duodenal microbial taxa, leading to decreased microbial diversity and increased relative abundance of coliforms and of anaerobic bacteria. The small intestine is vital to...
Source: Fight Aging! - October 10, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Better Mapping Age-Related Changes in the Human Gut Microbiome
In conclusion, this study examined how age and the process of aging are associated with changes in the microbiome of the small intestine, using validated sampling and processing techniques. The most significant differences are higher relative abundance of the phylum Proteobacteria and decreased relative abundance of Bacteroidetes in older subjects when compared to the youngest group. The higher relative abundance of Proteobacteria appeared to affect other duodenal microbial taxa, leading to decreased microbial diversity and increased relative abundance of coliforms and of anaerobic bacteria. The small intestine is vital to...
Source: Fight Aging! - October 8, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

More on NeuroD1 Gene Therapy to Restore Neural Function Following Injury and Scarring
You might recall that researchers have been working on the direct conversion of glial cells in the scars produced following ischemic injury to the brain. Overexpression of NeuroD1 via gene therapy appears an effective approach to achieve this goal, at least in the controlled scenario of an animal model. In mice this intervention gives rise to neurons that integrate into existing neural circuits, leading to some degree of functional recovery. We demonstrated that NeuroD1-mediated in vivo direct reprogramming of astrocytes into neurons promoted their neural circuit integration and led to the visual functional recove...
Source: Fight Aging! - October 8, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Senescent Mesenchymal Cells Cause Localized Inflammation in Osteoarthritic Cartilage
Given the failure of a locally injected senolytic drug to make a meaningful impact in osteoarthritis, the present consensus at the senolytics end of the longevity industry appears to be that systemic inflammatory signalling from senescent cells elsewhere in the body outweighs the contribution of local senescent cells in osteoarthritic joints. But perhaps the senolytic drug used in the failed trial was not a good candidate for humans; it remains to be seen as to whether better outcomes can be produced by systemic senolytic approaches in clinical trials for osteoarthritis. Meanwhile, researchers here suggest that there is in...
Source: Fight Aging! - October 8, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

On the Benefits of Estrogens in the Context of Longevity Differences by Gender
Why do women tend to live longer than men? There are a good many possible explanations for this well characterized observation. Gender differences in the pace of aging appears to be a robust outcome of the intersection of natural selection with a given mating strategy, but that doesn't say much about the specific mechanisms involved. Sex hormones are the obvious starting point for any investigation of the relevant molecular biology. In humans, estrogen provides numerous physiological benefits in addition to being a sex hormone, and so a higher estrogen level in women is a possible candidate mechanism. The tudy repor...
Source: Fight Aging! - October 7, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Age versus Frailty as a Predictor of Mortality
A number of companies and research groups are performing drug discovery by using effects on frailty in mice as a readout. To what degree is frailty an adequate measure of the harms done by aging? One way to answer that question is to assess mortality in a human study population against a measure of frailty, with and without factoring in chronological age. Researchers here show that frailty is a fair marker for age-related mortality, but it is not a reflection of every degenerative, harmful process taking place under the hood. Frailty and age combined provide a better correlation with mortality than frailty alone, indicatin...
Source: Fight Aging! - October 7, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Longevity Science Foundation Commits to $1 Billion in Research Funding Over the Next Decade
The inaugural press release from the Longevity Science Foundation touts their commitment to put $1 billion over the next ten years into research aimed at extending the healthy human lifespan, but is light on details as to where the funding is coming from. It is unclear as to how aspirational versus actual the proposal is. That said, the people involved are serious and successful scientist and entrepreneurs in the field, so we shall see. It is certainly the case that more sizable initiatives are needed, as well as more initiatives devoted to projects focused on the biotechnologies of rejuvenation, and not merely efforts to ...
Source: Fight Aging! - October 7, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Clarifying the Hyperfunction Theory of Aging
My encounters with the hyperfunction theory of aging have at times left me confused, and I suspect that not all of those arguing for it are working from exactly the same picture in their heads. The version presented in today's editorial is somewhat more clear, possibly because the primary intent of the paper is to clarify. It is worth noting up front that the author is very much a proponent of the centrality of mTOR and related signaling pathways in aging, in the sense that aging and age-related degeneration is a program of regulatory change that produces damage. The opposing mainstream viewpoint in the research community ...
Source: Fight Aging! - October 6, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Preprint of the Paper Summarizing the Leucadia Therapeutics Hypothesis and Evidence on the Cause of Alzheimer's Disease
The Leucadia Therapeutics staff has been working for a few years now to prove the founder's hypothesis on the cause of Alzheimer's disease. In this view, the primary problem is impaired drainage of cerebrospinal fluid. As the drainage path through the cribriform plate is blocked by slow ossification of channels, metabolic waste builds up in the olfactory bulb, the closest region of the brain. This is where Alzheimer's pathology initially starts, before spreading. The team has gathered an imposing amount of human anatomical data, and their eventual goal is to unblock the drainage path via an implant placed in the cribriform...
Source: Fight Aging! - October 6, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Icariin Treatment Improves the Aging Gut Microbiome in Mice
The gut microbiome is important in health and aging. Populations of microbes change with age, favoring harmful inflammatory populations at the expense of populations that generate beneficial metabolites. Restoration of a youthful microbiome via fecal microbiota transplantation has been demonstrated to be beneficial in animal studies. The research community is also evaluating other approaches to at least partially rejuvenate the aged gut microbiome, such as flagellin immunization to provoke the immune system into removing more of the harmful gut microbes. Researchers here provide evidence for treatment with icariin, a plant...
Source: Fight Aging! - October 6, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Aging as an Emergent Phenomenon, All Trees and No Forest
Theory and modeling dominates the study of the evolution of aging, as is the case in any field in which one is presented with a snapshot of a very complex environment and no ability to conduct directly relevant experiments on that environment. Beyond the state of the natural world here on earth, astrophysics is another good example: a zoo of diverse phenomenon out there in the universe and a great deal of highly mathematical back and forth here on Earth over exactly why the night sky looks the way it does. Given the nature of the field, any discussion of the fine details of the evolution of aging should be taken as ...
Source: Fight Aging! - October 5, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

How Much of the Benefit of a Healthier Diet is Due to Natural Calorie Restriction Mimetics?
How much of the benefit of a healthier diet arises from the effects of natural calorie restriction mimetic compounds? That question is an interesting one from a scientific perspective, but the answers are probably not all that valuable in a practical sense. We have a fairly good idea as to the size of the benefits to long-term health obtained via a better diet, and separately by eating less of that diet, the practice of calorie restriction while still obtaining sufficient micronutrients. Calorie restriction mimetic compounds trigger some of the same beneficial cellular stress response mechanisms as does a low calorie diet,...
Source: Fight Aging! - October 5, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Radiation Treatment Persistently Alters Heart Cell Function to Produce Benefits in Heart Failure Patients
This paper is interesting as a first step on the way to further research into compensatory therapies that can reduce the cardiac muscle dysfunction of heart failure. One-time radiation therapy appears to persistently change cardiomyocyte behavior via altered epigenetic regulation of notch signaling, leading to modestly improved heart tissue function. Perhaps this should be taken as supportive of efforts to more directly target this regulatory pathway in the aging heart via other means. Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). T...
Source: Fight Aging! - October 5, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

A Popular Science Article on Young Blood versus Old Blood in the Development of Treatments for Aging
The popular science article I'll point out today does a fair job of following the past decade or so of work arising from heterochronic parabiosis, in which the circulatory systems of a young animal and an old animal are joined. The young animal exhibits some degree of accelerated aging, while the old animal exhibits some degree of rejuvenated function. The question all along has been why exactly this happens: what are the underlying mechanisms, and can they be replicated as a basis for therapy. The obvious first approach was to transfuse young donor blood into old recipients, as positive results would mean that the ...
Source: Fight Aging! - October 4, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Treadmill Training for Old Mice Upregulates Autophagy and Improves Heart Function
It is well demonstrated that structured exercise programs improve function and reduce mortality in old humans, in part because the majority of people do not undertake anywhere near enough exercise. For mice, more activity takes place into later life, but how much is quite dependent on the environment in which they are housed. Looking at the study here, I would expect this to be a comparison of exercise trained mice with untrained mice that are less active than they would be if given options such as an exercise wheel. That may be a better match to the human situation than the other options. While looking at the results, it ...
Source: Fight Aging! - October 4, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Well Structured Cartilage Grown from Embryonic Stem Cells
Tissue engineering of new cartilage is an important goal in the field of regenerative medicine, but it has proven challenging to obtain the necessary structural properties. Natural cartilage is a resilient, strong tissue. Incremental progress towards this goal has been made over the years, as researchers explored the space of the possible. Now we see demonstrations such as the one noted here, in which sizable sections of engineered cartilage can be produced from embryonic stem cells, and the tissue exhibits the desired structural properties. If this can be achieved with embryonic stem cells, then it can in principle also b...
Source: Fight Aging! - October 4, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, October 4th 2021
In conclusion, premature thymic involution and chronic inflammation greatly contribute to increased morbidity and mortality in CKD patients. Mechanisms are likely to be multiple and interlinked. Even when the quest to fountain of youth is a pipe dream, there are many scientific opportunities to prevent or to, at least in part, reverse CKD-related immune senescence. Further studies should precisely define most important pathways driving premature immune ageing in CKD patients and best therapeutic options to control them. Extending Life Without Extending Health: Vast Effort Directed to the Wrong Goals https://www...
Source: Fight Aging! - October 3, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Preclinical Atherosclerosis is Widespread in 50+ Year Old People
Atherosclerosis is the growth of fatty, inflamed deposits in blood vessel walls, narrowing and weakening them. It results from processes that are universal, present in every older individual. The oxidative stress and inflammation of aging lead to a raised amount of oxidized lipids and lipid carriers such as LDL particles, and these produce a growing dysfunction in the macrophage cells responsible for clearing unwanted lipids from blood vessel tissue. It is not surprising to see the data presented in today's research materials, showing that near half of older adults in their 50s and 60s age have measurable atheroscle...
Source: Fight Aging! - October 1, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Genetic Variants Associated with Visceral Fat Accumulation Correlate with Longevity
It is well established that excess visceral fat is harmful. This tissue is metabolically active, and generates increased chronic inflammation through numerous mechanisms: a greater number of senescent cells; signaling by fat cells that appears similar to that produced by infected cells; increased debris from dead and dying fat cells that provokes the immune system. Overweight and obese people have a shorter life expectancy, greater incidence of age-related disease, and higher lifetime medical costs, with these disadvantages increasing with a larger burden of visceral fat tissue. It is not surprising, therefore, to find tha...
Source: Fight Aging! - October 1, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Cerebral Small Vessel Disease as a General Microvascular Issue Rather than a Specifically Atherosclerotic Issue
The aging of large blood vessels in the brain, and their resulting dysfunctions, are quite different from those of the small vessels, the microvasculature. Large vessels are predominantly affected by atherosclerosis, the buildup of fatty plaques that weaken and narrow blood vessels, leading to the catastrophic structural failure of a stroke. Small vessels, on the other hand, appear to be affected by a collection of mechanisms that cause functional deterioration, such as pathological amyloid deposition, with atherosclerosis as only one of that list of harmful processes. This is the point made in the open access paper here, ...
Source: Fight Aging! - October 1, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Extending Life Without Extending Health: Vast Effort Directed to the Wrong Goals
It is very hard to coax a damaged machine into continued operation without repairing the damage. It is expensive and time-consuming, the machine works poorly, and fails catastrophically only a little later than it would have done without all of that effort. Keeping damaged machines running is exactly the goal of near all work on treating age-related disease, however. Very few projects are focused on addressing the cell and tissue damage that causes aging. Anything other than repairing or otherwise reversing that damage will produce only marginal gains, at great expense. This has been well demonstrated. With the best...
Source: Fight Aging! - September 30, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Better Diet and Exercise Choices Slow the Progression of Epigenetic Aging in Distinct Ways
Epigenetic clocks were developed by correlating observed changes in DNA methylation with age. Aging produces characteristic changes in cell behavior due to damage and dysfunction. While the nature of these changes is the same in every individual, the pace at which aging processes differs somewhat, the result of differing lifestyle choices and environmental exposures, such as particulate air pollution and persistent viral infection. When measured epigenetic age is greater than chronological age, this is referred to as epigenetic age acceleration, and this appears to be a useful measure of the degree to which an individual i...
Source: Fight Aging! - September 30, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Using DNA Methylation to Determine Lobster Age
Until fairly recently, it was impossible to accurately determine the age of a lobster found in the wild. This is one of a number of marine species that exhibits negligible senescence, meaning few signs of aging across the majority of its lifespan. How long can a lobster live? That used to be quite unclear until it was found that it is possible to count growth rings in the eye stalks in order to age specimens caught in the wild. There is an ongoing process of aging in this species, despite their negligible senescence, as demonstrated here. Researchers have been able to correlate lobster age to changes in DNA methylation, in...
Source: Fight Aging! - September 30, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Chronic Kidney Disease and an Accelerated Aging of the Immune System
In conclusion, premature thymic involution and chronic inflammation greatly contribute to increased morbidity and mortality in CKD patients. Mechanisms are likely to be multiple and interlinked. Even when the quest to fountain of youth is a pipe dream, there are many scientific opportunities to prevent or to, at least in part, reverse CKD-related immune senescence. Further studies should precisely define most important pathways driving premature immune ageing in CKD patients and best therapeutic options to control them. (Source: Fight Aging!)
Source: Fight Aging! - September 29, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Borrowing Concepts from Particle Physics to Better Frame the Mechanisms of Aging
An interesting idea is put forward in this open access paper, aimed at producing a greater and more useful unity of thought about the processes of aging. It is certainly the case that the field lacks a common conceptual foundation to build upon when it comes to working towards a better understanding of the mechanisms of aging. Hence the many theories of aging, focusing on quite different areas of molecular biology and evolutionary biology, and the persistent debate over whether aging is an evolved epigenetic program of late life dysfunction (the minority position), or an accumulation of damage that falls outside selection ...
Source: Fight Aging! - September 29, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Senolytics as a Potential Treatment for Precancerous Lesions
It is reasonable to think that intermittent treatment with senolytics can suppress cancer incidence by killing the senescent cells that are present in precancerous lesions, whether or not they are too small to be identified by present screening techniques. This should reduce the number of cells that can potentially go on to become cancerous, and also remove the contribution of senescent cell signaling to the growth and inflammatory status of the lesion. It should not be too challenging to prove this hypothesis in animal models, but prevention of cancer in the general sense is, unfortunately, a hard sell when it comes to cl...
Source: Fight Aging! - September 29, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Aubrey de Grey on Choosing the Right Research and Development Projects in the Treatment of Aging
There are many different potential approaches to the treatment of aging as a medical condition. It is a sad truth, however, that funding the wrong type of project will almost certainly fail to move the needle on human aging. Further, it is almost certainly the case that most present effort in research and development is going towards the wrong type of project. A majority of the projects that could lead towards treatments for aging are focused on upregulation of the cellular stress response mechanisms triggered by exercise, calorie restriction, hypoxia, heat, and the like. We have a good idea as to the likely outcome of suc...
Source: Fight Aging! - September 28, 2021 Category: Research Authors: Reason Tags: Activism, Advocacy and Education Source Type: blogs

Harmful and Beneficial Roles for the Adaptive Immune System in Neurodegenerative Conditions
To a first approximation, cells of the adaptive immune system are barred from the brain by the blood-brain barrier. This is only a first approximation, however, and more careful research has shown that a small number of adaptive immune cells do in fact enter the brain. This appears to be the case throughout life, a part of the normal interaction between immune system and central nervous system. The presence of adaptive immune cells in the brain in later life is also thought to be pathological, however, the result of age-related dysfunction of the blood-brain barrier, allowing unwanted cells into the brain to cause harm. ...
Source: Fight Aging! - September 28, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Towards Better Cancer Vaccines via Identification of Important Neoantigens and T Cell Populations
Tumor cells have identifying surface markers that the immune system can in principle attack, but vaccination against those surface markers in order to encourage an anti-tumor immune response has been hit and miss. Researchers here dig deeper into the mechanisms that may explain this variability in response, and thus allow a more viable approach to patient-specific cancer vaccines that will more effectively rouse the immune system to target cancerous cells. When cells begin to turn cancerous, they start producing mutated proteins not seen in healthy cells. These cancerous proteins, also called neoantigens, can aler...
Source: Fight Aging! - September 28, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Rejuvenome Project Seeks to Carry Out Combined Longevity Intervention Studies in Mice
The Rejuvenome project at the Astera Institute aims to fill an important gap in research and development aimed at the slowing or reversing mechanisms of aging. Very little work in academia or industry assesses the outcome of combined treatments. Are several different senolytic drugs targeting difference mechanisms of senescent cell death, at lower doses, much better than just one senolytic drug, at a higher dose, at clearing harmful senescent cells from old tissues? Do aged mice live longer in good health with senolytics to remove senescent cells plus flagellin immunization to improve the gut microbiome plus exosome therap...
Source: Fight Aging! - September 27, 2021 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Calorie Restriction Improves Stem Cell Function
Researchers here briefly review the ability of calorie restriction to improve stem cell function in various different tissues over the course of aging. This is thought to be one of the ways in which the practice of calorie restriction slows aging, quite significantly in short-life species, and much less so in longer-lived species. Since the short-term metabolic changes, and benefits to health, produced by calorie restriction are quite similar across mammals of different life spans, it remains an open question as to exactly why life expectancy is only modestly affected in long-lived species. Calorie restriction induces swee...
Source: Fight Aging! - September 27, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Responses to Age-Slowing Interventions Differ by Organ and Gender
Once one starts to investigate, tissue type by tissue type, the effects of interventions known to modestly slow aging, one finds differences. This could be a matter of differences in the biodistribution of a particular therapeutic agent, or it could be that various forms of age-related damage are more or less significant in different organs, or that the regulation of stress responses differs from tissue to tissue, such that some therapeutics target a regulatory pathway more relevant to a kidney than a lung, for example. All of this implies that great deal of work lies ahead, if every potential therapy must be mapped by its...
Source: Fight Aging! - September 27, 2021 Category: Research Authors: Reason Tags: Daily News Source Type: blogs