An Interview with Hanadie Yousef of Juvena Therapeutics
The Life Extension Advocacy Foundation volunteers here interview Hanadie Yousef of Juvena Therapeutics. Her team is mining the secretions of pluripotent stem cells to find factors that can improve regeneration and stem cell activity in older individuals. Juvena represents one small slice of a broad trend in the regenerative medicine community, many teams building on the past decades of work on stem cell transplantation by seeking to understand and manipulate the cell signaling thought to produce benefits in patients undergoing these first generation therapies. In near all such stem cell therapies, the transplanted cells di...
Source: Fight Aging! - February 17, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Epigenetic Profile of Werner Syndrome is Very Different from that of Aging
The research community has long used progeroid syndromes such as Hutchinson-Gilford progeria syndrome and Werner syndrome as tools in the investigation of aging. This category of conditions are colloquially thought of as accelerated aging, but are in fact only a little similar to aging. The various underling genetic causes of progeria result in accelerated accumulation of cellular damage of various sorts, different in each case, leading to tissue dysfunction and outcomes that resemble a range of normal age-related conditions. Aging is itself a process of damage accumulation, so it isn't surprising to find some degree of si...
Source: Fight Aging! - February 17, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, February 17th 2020
Discussion of the Evolutionary Genetics of Aging Thymic Involution Contributes to Immunosenescence and Inflammaging The Potential for Exosome Therapies to Treat Sarcopenia Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice The Aging Retina, a Mirror of the Aging Brain Evidence for Loss of Capillary Density to be Important in Heart Disease Aspects of Immune System Aging Proceed More Rapidly in Men Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation Transplantation of Senescent Cells is an ...
Source: Fight Aging! - February 16, 2020 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

PTTG1 as Prompt for Discussion of the Evolutionary Genetics of Aging
Aging is under genetic control in the sense that species have different genomes, different life spans, and different manifestations of aging within those life spans. Within any given species, it is far from clear that genetic variation has a large enough influence to care about. Individuals vary, but the evidence strongly suggests that this is near all due to environmental rather than genetic differences. Where there are genetic differences, the old who survive to benefit from them are still old people, greatly impacted by aging and trapped in a downward spiral of dysfunction. The author of this commentary uses the ...
Source: Fight Aging! - February 14, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Transplantation of Young Bone Marrow into Old Mice Produces Systemic Benefits
Researchers here report that transplanting bone marrow from young donor mice into old recipient mice produces a range of benefits, such as improvement in the behavior of macrophage cells. Bone marrow stem cells are responsible for producing blood and immune cells, among other important populations, and this capability is degraded in a number of ways with age. Introducing younger stem cells and their supporting structures is a plausible means to at least partially reverse this process. That said, this sort of approach is unlikely to arrive in human medicine in exactly the same form, given the challenges involved in bone mar...
Source: Fight Aging! - February 14, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Transplantation of Senescent Cells is an Issue in First Generation Stem Cell Therapies
Researchers here demonstrate that comparatively simple regenerative cell therapies, of the sort presently widely used, in which stem cells are derived from adipose tissue, will tend to introduce senescent cells into the recipient in the case of older donors. Senescent cells are constantly created and destroyed in the body, but the processes of clearance decline with age, and these cells are harmful when they linger for the long term: their secreted signals cause chronic inflammation, while also contributing to tissue dysfunction in a number of other ways. The presence of senescent cells in older individuals is one of the c...
Source: Fight Aging! - February 14, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Video and Transcript of Aubrey de Grey Presenting to the Effective Altruism Community
Aubrey de Grey administers the scientific programs at the SENS Research Foundation, and is a leading figure in the rejuvenation research community and newly formed longevity industry. Here find a transcript of his present commentary on the state of rejuvenation research, lightly tailored for delivery to an audience of effective altruists. Effective altruism is a useful movement, I feel, if nothing else for the pressure that advocates might bring to bear on the corruption and ineffectiveness of much of present day institutional philanthropy. Further, while it might seem self-evident to much of the Fight Aging! audience that...
Source: Fight Aging! - February 13, 2020 Category: Research Authors: Reason Tags: Healthy Life Extension Community Source Type: blogs

Deacetylation of the NLRP3 Inflammasome as a Way to Control Chronic Inflammation
Chronic inflammation is an important component of degenerative aging. Excessive inflammatory signaling and activation of the immune system arises due to a combination of many factors, of which some are more important than others, such as the presence of lingering senescent cells. Most of the research focused on controlling inflammation is more interested in sabotaging the mechanisms of control than in removing root causes, however. The work here is an example of the type, in which scientists identify an important feature of the regulatory system controlling inflammation. Forcing a sizable reduction of inflammation via this...
Source: Fight Aging! - February 13, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Aspects of Immune System Aging Proceed More Rapidly in Men
Men do not live as long as women. This is a consistent effect across populations and eras, and there are any number of theories as to why this is the case. This might lead us to expect measurable aspects of aging to be more pronounced in older males than in older females, and researchers here show that this is the case for the age-related dysfunction of the immune system. As we age, the immune system becomes both overactive and less capable, leading to chronic inflammation alongside decreased resistance to infection and cancer. This is an important contribution to age-related frailty, disease, and mortality. Human...
Source: Fight Aging! - February 13, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Prospects for Telomerase Gene Therapy as a Treatment for Heart Disease
Telomerase gene therapy is considered in some quarters to be a viable treatment for aging. Telomeres are the caps of repeated DNA sequences at the ends of chromosomes. They are an important part of the mechanism limiting the number of times that somatic cells in the body can divide, the Hayflick limit. A little telomere length is lost with each cell division, and short telomeres trigger cellular senescence or programmed cell death, halting replication. Stem cell populations use telomerase to lengthen their telomeres and thus self-renew to provide a continual supply of new somatic daughter cells with long telomeres to repla...
Source: Fight Aging! - February 12, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Evidence for Loss of Capillary Density to be Important in Heart Disease
Loss of capillary density, and thus flow of blood through tissues, is a known feature of aging, though the causes of this change in tissue maintenance are far from completely explored. It is proposed to be quite important in loss of tissue function, particularly in organs with high metabolic demands, such as muscle and the brain. Researchers here provide evidence to suggest that this loss of capillary density is a noteworthy mediating mechanism linking the age-related impairment of heart function with the presence of chronic kidney disease. The latter is already known to correlate with impaired capillary structure in the h...
Source: Fight Aging! - February 12, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Aging Retina, a Mirror of the Aging Brain
Retinal degeneration is a feature of old age, and here researchers show that it correlates quite well with a loss of volume in portions of the visual cortex of the aging brain. These two portions of the nervous system are are connected and related, but it is unclear as to whether there is a direction of causation, or whether this is a case of similar structures being similarly affected by the same underlying mechanism of aging. Chronic inflammation, for example, operates throughout the body, and many aspects of aging are correlated because inflammation accelerates tissue dysfunction in a systemic, whole-body manner. ...
Source: Fight Aging! - February 12, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Nicotinamide Riboside Improves Hematopoiesis and Immune Cell Populations in Mice
Mitochondria are the power plants of the cell. They produce the chemical energy store molecule ATP that is used to power cellular operations. Unfortunately, mitochondrial function falters throughout the body with advancing age, and while this is harmful in all tissues, the effects are particularly problematic in energy-hungry tissues such as the muscle and brain. Research of recent years has implicated the loss of nicotinamide adenine dinucleotide (NAD+) in mitochondria in this process. Evidence suggests that loss of effectiveness in mitophagy, the process that recycles worn and damaged mitochondria, is the important issue...
Source: Fight Aging! - February 11, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Evidence for PASK Deficiency to Reduce the Impact of Aging in Mice
There are many ways to slow aging to a measurable degree in short-lived species such as mice, and the work noted here is a recently discovered example. Mice have evolved to have a sizable variability of life span in response to environmental circumstances, and thus the cellular machinery relating to various stress responses has an equally sizable influence on health and longevity. Since there are many ways to adjust the operation of that machinery, by increasing or decreasing levels of specific proteins, there are also many ways to slow aging. Few of them are going to be all that useful, unfortunately, as longer-lived spec...
Source: Fight Aging! - February 11, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Correlations of Mitochondrial DNA Copy Number and Epigenetic Age Measures
Mitochondria are the power plants of the cell, a herd of bacteria-like organelles that produce the chemical energy store molecule ATP. They have their own DNA, a circular genome distinct from that of the cell nucleus, sometimes several copies per mitochondrion. The number of those mitochondrial DNA copies in a cell is a measure of mitochondrial health that declines with age, as mitochondria become dysfunctional throughout the body. The proximate causes of this dysfunction involve changes in mitochondrial structure and dynamics that inhibit the quality control process of mitophagy, responsible for recycling worn and damaged...
Source: Fight Aging! - February 11, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Notes on the 2020 Longevity Therapeutics Conference in San Francisco
I recently attended the 2020 Longevity Therapeutics conference in San Francisco. I presented on the work ongoing at Repair Biotechnologies, but as is usually the case the more important parts of the visit took place outside the bounds of the conference proper. Longevity Therapeutics is one of the four or five core conferences for the longevity industry, at which you'll meet many of the early participants - a mix of scientists, entrepreneurs, and investors, and patient advocates. As such, most of the conference goers have already seen my updates, or are otherwise aware of the Repair Biotechnologies programs aimed at thymic ...
Source: Fight Aging! - February 10, 2020 Category: Research Authors: Reason Tags: Healthy Life Extension Community Source Type: blogs

The Potential for Exosome Therapies to Treat Sarcopenia
The authors of this open access review walk through some of the evidence for delivery of exosomes, such as those derived from stem cells, to be a basis for treating sarcopenia. Sarcopenia is the progressive loss of muscle mass and strength that takes place with aging. While a fair degree of sarcopenia is preventable, being the consequence of an age of comfort, leisure, and too little exercise, the rest of it is still inevitable absent some way to interfere in the mechanisms of aging that disrupt muscle tissue maintenance. The delivery of cell signals encapsulated in exosomes might be capable of forcing muscle stem cells in...
Source: Fight Aging! - February 10, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Thymic Involution Contributes to Immunosenescence and Inflammaging
The thymus is an underappreciated organ, responsible for the complex process of generating mature T cells of the adaptive immune system. Unfortunately it atrophies with age in a process called thymic involution. By age 50 most people have little active thymic tissue left. They must coast for the rest of their lives on the adaptive immune cells that they have at that point, replicating in the periphery of the body without a meaningful supply of new reinforcements. This inevitably leads to an immune system made up of damaged, overspecialized, and malfunctioning cells, incapable and inflammatory. That part of the overa...
Source: Fight Aging! - February 10, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, February 10th 2020
In conclusion, the concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. A Discussion of Recent Work on Allotopic Expression of Mitochondrial Genes at the SENS Research Foundation https://www.fightaging.org/archives/2020/02/a-discussion-of-recent-work-on-allotopic-expression-of-mitochondrial-genes-at-the-sens-research-foundation/ A paper published last month outlines recent progress on allotopic expression of mitochondrial genes carried out by the SENS Research ...
Source: Fight Aging! - February 9, 2020 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Two Examples of UK Biotech Startups Focused on the Treatment of Aging
The biotech startups of the core longevity industry, founded by the entrepreneurs who are regulations in the English-language conference circuit, are largely US companies. This is the way of the world in the biotech industry in general. The non-US participants include startups of British, Russian, and other origins, though it is often the case that when a company achieves some success it moves to where its backers and allies are found. For reasons relating to the historical interests of local research communities, and current interests of local venture funds, companies tend to be clustered in a few countries rather than be...
Source: Fight Aging! - February 7, 2020 Category: Research Authors: Reason Tags: Investment Source Type: blogs

Exceptionally Long Lived Humans Exhibit Slower Epigenetic Aging, Measured by DNA Methlyation Clocks
Epigenetic clocks are produced by examining age-related changes in DNA methylation, finding combinations of such changes that are consistent across populations, and predict chronological age. These clocks also predict mortality, in the sense that people with higher epigenetic than chronological age tend to have a higher mortality risk, or be more burdened by chronic age-related disease. The challenge here is that it remains very unclear as to what these epigenetic clocks are actually measuring, which of the underlying processes of aging they reflect, and to what degree. That makes it hard to use epigenetic clocks in any me...
Source: Fight Aging! - February 7, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Reviewing Efforts to Develop NAD+ Therapies to Reverse Age-Related Loss of Mitochondrial Function
Increasing levels of NAD+ in mitochondria, is a class of therapy that probably produces most of its benefits in animal models and human trials by restoring mitophagy. This may well be true of mitochondrially targeted antioxidants as well. Mitophagy removes damaged mitochondria, but is hampered by age-related changes in mitochondrial dynamics, among other reasons. Mitochondria are responsible for packaging chemical energy store molecules to power cellular operations. Mitochondrial function is critical to tissue function throughout the body, but is of particular note in the energy-hungry tissues of muscle and brain. N...
Source: Fight Aging! - February 7, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

More Data on the Tissue Specificity of Senescent Cell Accumulation with Age in Mice
In this study, we provide a comprehensive measure of senescence in aged wild type (WT) mice. Senescence was quantified in multiple tissues, using numerous methods and numerous molecular endpoints, and we compared measures with that of young adult WT mice. We used this as a benchmark to determine whether Ercc1-/∆ mice, that exhibit accelerated aging, accumulate senescent cells in physiologically relevant tissues. As measured by qRT-PCR and p16LUC signal, levels of p16Ink4a were significantly increased in aged WT mice compared with younger adult mice, as expected, p16Ink4a and p21Cip1 expression are found in periphe...
Source: Fight Aging! - February 6, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Endothelial Cell Senescence can Impair Insulin Sensitivity
The growing presence of senescent cells contributes to near all of the declines and tissue dysfunctions of aging, judging by the results produced in extensive research carried out in animal models of age-related disease. Senescent cells secrete a mix of inflammatory and other signals that, when present for the long term, cause considerable harm to tissue structure, function, and maintenance. The research here is focused on just one form of dysfunction, but is illustrative of many other studies in the field of senescence carried out in recent years. Endothelial cells (ECs) line the inner surface of blood vessels, a...
Source: Fight Aging! - February 6, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Long Non-Coding RNAs and Macrophage Senescence in Age-Related Disease
Here, researchers review cellular senescence in macrophage cells and the biochemistry of long non-coding RNAs in macrophage senescence, a topic of great relevance to a number of age-related conditions, such as atherosclerosis. Cellular senescence takes place in most cell populations, in response to reaching the Hayflick limit on replication or in response to stress and damage. Senescent cells have important short-term roles to play, and near all destroy themselves or are destroyed by immune cells soon after entering the senescent state. These cells become harmful when they linger over long term, however, even in comparativ...
Source: Fight Aging! - February 6, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Macrophages Implicated in the Scarring of Heart Tissue Following Injury
A potentially important faction within the regenerative medicine community is engaged in trying to understand exactly how highly regenerative species such as salamanders and zebrafish can regenerate organs following injury, and do so repeatedly without scarring. There are also a few examples of adult mammals capable of regenerating a limited number of body parts without scarring, such as African spiny mice and the MRL mouse lineage. It seems plausible that mammalian species still carry much of the machinery of proficient regeneration, but that this machinery is suppressed in some way, possibly because that suppression acts...
Source: Fight Aging! - February 5, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Mechanism by which Chronic Inflammation Spurs Cancer Metastasis
Chronic inflammation is a risk factor for cancer and cancer mortality. There are numerous reasons as to why this might be the case, some much more proven and settled than others, but the research here is focused on metastasis, the spread of cancerous cells throughout the body. Since cancer mortality is largely determined by whether or not a tumor progresses to the point of metastasis, we should not be surprised that researchers can identify mechanisms linking inflammation with metastasis. Dysregulated inflammation is recognized as one of the hallmarks of cancer and is involved in tumor initiation, progression, an...
Source: Fight Aging! - February 5, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

An Example of Epigenetic Effects on Offspring Longevity
It was discovered only comparatively recently that epigenetic alterations, decorations attached to the genome rather than changes to the genome itself, can produce changes in offspring longevity. Not all epigenetic changes are erased during early embryonic development; some are retained and go on to influence development and metabolism throughout life. This is a mechanism by which species can improve their reproductive fitness via producing offspring better suited to the environment experienced by the parents. One of the best examples is that calorie restriction affects the metabolism and longevity of the offspring of anim...
Source: Fight Aging! - February 5, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Chronic Inflammation is of Great Importance in the Progression of Aging
We describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants, and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI. (Source: Fight Aging!)
Source: Fight Aging! - February 4, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Modulating Macrophage Polarization as a Therapy for Atherosclerosis
In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/- mouse model and RAW 264.7 macrophages exposed to oxidized LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in oxidized-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methylad...
Source: Fight Aging! - February 4, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Mechanisms of Slowed Muscle Aging via Calorie Restriction in Rhesus Macaques
Many of the readers here will be familiar with the very long-running studies of calorie restriction in rhesus macaques. There was some discussion of the data a few years ago. The research has continued since then, and here researchers report on their investigation of the biochemistry of calorie restriction in connection to the slowed aging of muscle tissue observed in these animals. Calorie restriction produces sweeping changes in the operation of cellular metabolism, and aging is itself a very complex process, even though it stems from simpler root causes. Research into the tissue-specific details of how and why calorie r...
Source: Fight Aging! - February 4, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Forcing Macrophages into Greater Clearance of Debris in Atherosclerotic Lesions
Atherosclerosis is the generation of fatty deposits in blood vessel walls, called plaques, atheromas, or lesions, that narrow and weaken important vessels. Sooner or later a vessel ruptures, or a plaque disintegrates and its fragments block the flow of blood, and this results in stroke or heart attack. In the public eye atherosclerosis is considered a disease of cholesterol, of blood lipids, and reducing cholesterol and other lipids in the blood remains the primary focus of treatment. This is despite the fact that this approach can only slow progression - it doesn't reverse existing lesions to a sizable degree. Athe...
Source: Fight Aging! - February 3, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Discussion of Recent Work on Allotopic Expression of Mitochondrial Genes at the SENS Research Foundation
A paper published last month outlines recent progress on allotopic expression of mitochondrial genes carried out by the SENS Research Foundation team. Allotopic expression is the name given to the process of putting copies of mitochondrial genes into the nuclear genome, suitably altered to allow proteins to be generated and shipped back to the mitochondria where they are needed. Mitochondria replicate like bacteria, and some forms of stochastic mitochondrial DNA damage can make mitochondria both dysfunctional and able to outcompete their undamaged peers. This is thought to be an important contribution to aging, resulting a...
Source: Fight Aging! - February 3, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Evidence for the Epigenetic Clock to Underestimate Age in Later Life
In conclusion, the concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate. Link: https://doi.org/10.1186/s13059-019-1810-4 (Source: Fight Aging!)
Source: Fight Aging! - February 3, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, February 3rd 2020
In conclusion, this study suggests that epigenetic age acceleration is significantly associated with lung function in women older than 50 years. We hypothesised that this could be due to menopause. However, we have observed that menopause has minimal effect and therefore there is possibility of other unknown physiological factors at older age in females mediating the epigenetic age acceleration effect on lung function. While, it is still unknown what exactly epigenetic aging from DNA methylation measures, this study suggests it can be utilised as one of the important factors to assess women's lung health in old age. DNA me...
Source: Fight Aging! - February 2, 2020 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Loss of Lung Function Correlates with Epigenetic Age Acceleration
In conclusion, this study suggests that epigenetic age acceleration is significantly associated with lung function in women older than 50 years. We hypothesised that this could be due to menopause. However, we have observed that menopause has minimal effect and therefore there is possibility of other unknown physiological factors at older age in females mediating the epigenetic age acceleration effect on lung function. While, it is still unknown what exactly epigenetic aging from DNA methylation measures, this study suggests it can be utilised as one of the important factors to assess women's lung health in old age. DNA me...
Source: Fight Aging! - January 31, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Loss of Volume in the Cerebellum Correlates with Memory Decline with Age
The brain is known to shrink with age, by about 5% per decade in later adult life, though the underlying processes leading to this loss of volume are not well understood in detail. The research here adds to existing evidence for loss of volume to correlate with loss of cognitive function. It is unclear as to what can be done specifically to address this issue beyond developing the means to repair the list of damage and dysfunction that causes aging, and observing the results as repair therapies are deployed, first in animals, and then in humans. The human cerebellum plays an essential role in motor control, is inv...
Source: Fight Aging! - January 31, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

A Guide Implant Allows Regrowth of Inches of Lost Nerve Tissue
Severed nerves left with a significant gap between the ends do not regrow in adult mammals. Scarring rather than regeneration takes place, and loss of function is permanent. All is not bleak, however. Researchers here report on progress in guided nerve regrowth, using a implant that encourages regeneration of nerve tissue across a comparatively large distance. The prospects for recovery from damage to the peripheral nervous system are becoming brighter. Assuming it is accompanied by removal of scar tissue at the nerve ends, the regenerative approach illustrated here could, in principle, be applied well after an injury has ...
Source: Fight Aging! - January 31, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Cellular Senescence in the Bone Marrow as a Contributing Cause of Osteoporosis
Cellular senescence contributes meaningfully to near all age-related conditions, judging by the research of the past few years. In only a very few cases has clearance of senescent cells failed to perform well as a basis for therapy. In just the past year, papers have been published on the role of senescent cells in twenty or more very different age-related conditions. In many cases, the researchers demonstrated that clearance of a sizable fraction of the senescent cells present in tissues, using one of the available senolytic mouse models or small molecule therapies, reversed the progression of the age-related condition un...
Source: Fight Aging! - January 30, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

The Role of Lipids in Metastasis Offers Therapeutic Targets that May Work for Many Cancers
The primary mechanism by which most cancers kill patients is metastasis, the spread of cancerous cells from the original tumor to new locations throughout the body. If metastasis didn't exist, cancer would be a much more tractable problem, largely capable of being controlled via even the blunt approach of surgery. Research that might lead to ways to sabotage metastasis across many different types of cancer is thus of great interest. A number of possible approaches have emerged over the past decade or so, but none have as yet advanced to the point of practical application in the clinic. Researchers have demonstrate...
Source: Fight Aging! - January 30, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Dicer1 Gene Therapy as a Treatment for Age-Related Macular Degeneration
This study also suggests that restoring DICER1 expression in the retina could itself be a viable therapeutic target for the treatment of AMD. Link: https://doi.org/10.1073/pnas.1909761117 (Source: Fight Aging!)
Source: Fight Aging! - January 30, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

The Concept of Successful Aging is Harmful to Research and Development
As illustrated in today's research commentary, all too many researchers continue to view aging as something distinct from age-related disease, and this inevitably leads to a poor approach to research and development. In this case, a rejection of the idea that rejuvenation is possible in principle at the present time. If one believes that aging and age-related disease are distinct, then one can also think that it is possible to age successfully, or age healthily. That we should split out the concepts of aging and disease, and only treat disease. This is all abject nonsense. There is no such thing as healthy aging or success...
Source: Fight Aging! - January 29, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Senolytic Treatment Fails to Reverse Uterine Fibrosis in Mice
Senolytic drugs that selectively destroy senescent cells in aged tissues have performed quite well in animal studies of fibrosis in heart, lung, and kidney. The therapy reverses fibrosis in those tissues to a larger degree, and with greater reliably, than is the case for any other readily available approaches. Unfortunately small molecule senolytics are all tissue specific to varying degrees in their biodistribution and effects, and so the benefits are not universally realized throughout the body. As an example of this point, researchers here show that uterine fibrosis and its consequences are unresponsive to dasati...
Source: Fight Aging! - January 29, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Combination Gene Therapy for α-Klotho and TGFβR2 Improves Osteoarthritis in Mice
Researchers here report that upregulation of α-Klotho and TGFβR2 together, via gene therapy, can modestly reverse osteoarthritis in a rat model in which untreated animals progress to a more severe stage of the condition. Inhibiting TGF-β receptors such as TGFβR2 is known to suppress chronic inflammation, and likely functions by interfering in the inflammatory TGF-β signaling produced by senescent cells. The evidence for cellular senescence to drive the progression of osteoarthritis is quite compelling at this point. Meanwhile, α-Klotho declines with age and upregulation of this protein is kn...
Source: Fight Aging! - January 29, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Macrophage Polarization in Aging is Complicated and Poorly Understood
Macrophages are a type of innate immune cell, and like all immune cells are involved in a great many processes in the body, ranging from tissue regeneration to clearing out molecular waste and debris to destruction of pathogens. Macrophages, and the similar microglia of the central nervous system, adopt different phenotypes, known as polarizations, depending on environment and the task at hand. The M1 polarization is pro-inflammatory and focused on ingestion of pathogens and debris, while the M2 polarization is anti-inflammatory and focused on regeneration. These are broad buckets and as such not truly representative of th...
Source: Fight Aging! - January 28, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Conservative View on Lifestyle versus Pharmacological Interventions for Aging
This open access commentary reflects a reasonable conservative position on the development of means to treat aging, which is that nothing can yet greater and more reliable results in humans than undertaking a better lifestyle. In this view, some combination of aerobic exercise, strength training, and calorie restriction robustly does more for most people than any of the other options on the table. Ten years ago I would have agreed. Now, however, I think it clear that, at the very least, senolytic therapies to selectively destroy senescent cells and some forms of mesenchymal stem cell transplantation, those capable of produ...
Source: Fight Aging! - January 28, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

More on the SASP Atlas, a Basis for Biomarkers of Aging
In the publicity materials here, researchers discuss the recently published SASP Atlas, a fairly comprehensive map of the molecules secreted by senescent cells - the senescence-associated secretory phenotype (SASP). Cells become senescent at the end of their replicative lifespan, but also in response to wounding, DNA damage, a toxic environment, or the signals of senescent neighbors. Senescence is transient, in the sense that these cells should self-destruct or be destroyed by the immune system shortly after their creation. Unfortunately these processes become inefficient with age, leading to rising numbers of senescent ce...
Source: Fight Aging! - January 28, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Calorie Restriction and Calorie Restriction Mimetics Dampen Inflammation
Chronic inflammation is an important aspect of aging, a process that stems from low-level biochemical damage and cellular dysfunction, and that then contributes to the progression of age-related disease and tissue dysfunction. Chronic inflammation sustained over years accelerates all of the common fatal age-related conditions: it disrupts tissue maintenance, and leads to fibrosis, immune dysfunction, and many more issues. The chronic inflammation of aging is important enough that beneficial therapies have been built on the basis of suppressing inflammation directly, without addressing its causes. Treatments that actually a...
Source: Fight Aging! - January 27, 2020 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Premature Menopause Correlates with Greater Later Incidence of Chronic Disease
Undergoing earlier menopause is a sign of a greater burden of age-related damage and dysfunction, so it should not be surprising to see that this correlates with a greater incidence of chronic disease in the years thereafter. People with a greater burden of cell and tissue damage tend to exhibit all of the manifestations of aging earlier than their less damaged peers. These variations in damage burden and consequences from individual to individual are near all the results of lifestyle choices, particularly smoking, weight, and exercise, and environmental factors such as exposure to chronic viral infection. Genetics plays o...
Source: Fight Aging! - January 27, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Astrocyte Senescence Causes Death of Neurons in Cell Culture
With the caveat that the behavior of cells in culture is not necessarily all that relevant to their behavior amidst the full complexities of living tissue, this study is an interesting initial exploration of the ways in which the cellular senescence of supporting cells in the brain might contribute to the progression of neurodegeneration. Senescent cells secrete a potent mix of inflammatory and other signaling; while they serve a useful purpose when present for a short time, not all are successfully destroyed. Their numbers grow with age, and the presence of these errant cells and their signaling is very harmful over the l...
Source: Fight Aging! - January 27, 2020 Category: Research Authors: Reason Tags: Daily News Source Type: blogs