Epigenetic Clocks Do Not Only Measure Epigenetic Drift
Epigenetic clocks are produced from data on the status of DNA methylation at CpG sites in the genome at various ages via machine learning processes. Thus it is unclear as to what the clocks actually measure. There is no catalog to state how and why each CpG site on the genome is or is not methylated at any given time. There is little to no understanding of the mechanistic links between specific epigenetic marks such as DNA methylation and specific mechanisms and states of aging. In that context, the work here is interesting, demonstrating that stochastic epigenetic dysregulation with age, known as epigenetic drift, contrib...
Source: Fight Aging! - February 14, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Allostatic Load as a Correlate of Aging
Allostatic load is the concept of wear and tear on the body that emerges from stresses via overactivation of the neuroendocrine system. Causative stresses can range from starvation to psychological stress to a high burden of age-related dysfunction. At some point reactions to stress that are compensatory tip over into being themselves damaging. Thus one could expect allostatic load to correlate with degenerative aging and risk of mortality to at least some degree. In practice, however, there is little agreement on how to measure allostatic load, particularly in human patients, which makes it hard to compare results from st...
Source: Fight Aging! - February 14, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Reviewing the Data on Human Use of Rapamycin
Rapamycin and some of the later rapalog derivatives such as everolimus, all of which function via inhibition of mTOR, are arguably the best of the present crop of geroprotective drugs capable of modestly slowing aging and extending life in animal studies. The effects of rapamycin in mice are robust and repeatable, though never as large as we'd all like them to be. Like many of the other interventions that modestly slow aging in animal models these small molecule drugs mimic some of the effects of calorie restriction, and likely produce benefits largely through increased efficiency of the cell maintenance processes of autop...
Source: Fight Aging! - February 13, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
The Skin Microbiome in Skin Aging
In comparison to presently expanding studies of the gut microbiome, much less effort is directed towards the skin microbiome in the context of aging. Given the existence of the sizeable and vocal cosmetics industry, I'm sure that will change in the years ahead, however. For now, research into mechanisms by which the skin microbiome might change with age and in turn affect the aging of skin remains lagging somewhat behind the equivalent programs focused on intestinal microbial populations and their effects on the aging body and brain.
The interplay between microbes and the skin barrier holds pivotal significance in...
Source: Fight Aging! - February 13, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Assessing the Influence of the Hallmarks of Aging
The objective of the present review has been to determine the impact of the Hallmarks and address if the purpose that gave them rise was achieved. For that aim, we reviewed the literature that cited any of the two versions of the Hallmarks. The conclusion was that the first version (with the second one also following the same trend) accomplished the goal, as it influenced a vast variety of fields ranging from the different areas of aging research to other related fields. Furthermore, it also inspired other authors and served as a model for the organization of knowledge, giving rise to a wide variety of "Hallmarks" in other...
Source: Fight Aging! - February 13, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Macrophages Disrupt Bone Regeneration by Provoking Stem and Progenitor Cell Senescence
In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers skeletal stem cell and progenitor cell (SSPC) senescence and impairs fracture healing. Local injection of human recombinant GCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of...
Source: Fight Aging! - February 12, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Oxidative Stress and Cellular Senescence in Alzheimer's Disease
In this paper, the authors discuss the overlap between oxidative stress and growing numbers of senescent cells in the brain. Both are thought to contribute to neurodegenerative conditions such as Alzheimer's disease. The aging of the brain is complex, a web of interacting processes, causes, and consequences. It has proven to be difficult to determine which processes are more or less important; the only efficient way forward is to come up with interventions that remove just one contributing factor with minimal side-effects. That is now possible for senescent cells, and clinical trials are underway, but manipulation of oxida...
Source: Fight Aging! - February 12, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Considering the Near Future of Senotherapeutics
Senescent cells accumulate with age, and this accumulation drives a sizable fraction of the dysfunction of degenerative aging. While never present in very large numbers, these cells energetically secrete signal molecules that provoke inflammation and tissue remodeling. As noted here, a major theme in the development of senotherapeutic drugs to either selectively destroy senescent cells or broadly suppress the disruptive signaling of senescent cells is the need for greater understanding of the diversity of cellular senescence. Different tissues, different cell types, different origins of the senescent state may all be meani...
Source: Fight Aging! - February 12, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Fight Aging! Newsletter, February 12th 2024
In conclusion, frailty is a dynamic process, and improved frailty and remaining robust are significantly associated with lower risk of all-cause mortality and cardiovascular death in older people.
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Greater Individual Wealth Correlates with Longer Life Expectancy
https://www.fightaging.org/archives/2024/02/greater-individual-wealth-correlates-with-longer-life-expectancy/
Individual wealth correlates with life expectancy, with an effect size that is in the same ballpark as those related to lifestyle choices involving exercise, diet, and consequences thereof. It remains unclear...
Source: Fight Aging! - February 11, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Reversing Age-Related Frailty Reduces Cardiovascular Risk and Mortality
In conclusion, frailty is a dynamic process, and improved frailty and remaining robust are significantly associated with lower risk of all-cause mortality and cardiovascular death in older people. (Source: Fight Aging!)
Source: Fight Aging! - February 9, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Bypassing Causes to Focus on Repairing Damaged Synapses in Alzheimer's Disease
Should we expect an approach focused on repair of synapses in neurodegenerative conditions like Alzheimer's disease, while leaving the causative mechanisms of the condition operating intact, to have a large effect on patient outcomes? Given what is known of the underlying mechanisms of protein aggregation, neuroinflammation, and other problems that ultimately kill neurons, not just damage them, it seems possible that synaptic repair might do well in the early stages of cognitive impairment, but later do little to help as the condition progresses. Regardless, it is interesting to consider to degree to which neural function ...
Source: Fight Aging! - February 9, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
IL-15 Improves the Ability of Natural Killer Cells to Attack Cancerous Tissue
Cancerous tissue co-opts the immune system, suppressing its ability to destroy cancerous cells, and even gaining the assistance of immune cells in encouraging the growth of a tumor. There are many different mechanisms by which this happens, varied by immune cell type and form of cancer, comparatively few of which are well mapped and well understood. The active and well-funded cancer research community continues to explore the potential to interfere in these harmful interactions between cancer and immune system. The approach noted here is one of many, and typical of this sort of research program in that it targets a specifi...
Source: Fight Aging! - February 9, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
The Death of Death, in English
The authors of the Death of Death are regulars on the conference circuit for aging research, the longevity industry, and patient advocacy for the treatment of aging as a medical condition. The book was originally in Spanish, and has finally been translated into English. It is a popular science overview of progress towards technologies that will first slow aging, then enable the control of aging, and eventually, at some point, produce large gains in healthy human life span, postponing death by aging essentially indefinitely. The book and its authors also unapologetically and straightforwardly stand in opposition to the horr...
Source: Fight Aging! - February 8, 2024 Category: Research Authors: Reason Tags: Activism, Advocacy and Education Source Type: blogs
Further Assessing the Effects of Air Pollution on Mortality
This study included 13,207 old participants with 73.3% aged 80 and beyond, followed up from 2008 to 2018 in 23 Chinese provinces. We used the Cox-proportional hazards model and quantile-based g-computation model to measure separate and joint effects of the multiple pollutants. We adjusted for climate and area economic factors based on a directed acyclic graph.
In 2018, no participants met the WHO AQG for PM2.5 and O3, and about one-third met the AQG for NO2. The hazard ratio (HR) for mortality was 1.07 per decile increase in all three pollutants, with PM2.5 being the dominant contributor according to the quantile-ba...
Source: Fight Aging! - February 8, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Glial Cell Senescence Impairs α-Synuclein Clearance, Contributing to Parkinson's Disease
In this study, we investigated how aging and glial senescence affect the capacity of α-syn clearance. We found that following the intra-striatal injection of human α-syn (hu-α-syn) preformed fibril, hu-α-syn pathology persisted more in aged mice compared with younger mice and that aged microglia exhibited greater accumulation of hu-α-syn than younger microglia. Moreover, in vitro assay revealed that the clearance of hu-α-syn was primarily dependent on the autophagy-lysosome system rather than on the ubiquitin-proteasome system and that the capacity of hu-α-syn clearance was diminished in senescent glia because of au...
Source: Fight Aging! - February 8, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
