An Aged Hematopoietic System can Cause Cognitive Decline via SASP Component CyPA

Today's open access paper outlines an investigation into how the aging of hematopoietic stem cell populations in bone marrow, responsible for producing blood and immune cells, can contribute to age-related dysfunction in the brain. The authors find that detrimental effects are mediated by circulating levels of CyPA, a signaling factor that is a part of the senescence-associated secretory phenotype (SASP), an inflammatory mix of signal molecules produced by senescent cells. The focus here is on direct inhibition of CyPA as an approach to therapy, but senolytic treatments to clear senescent cells may be the more useful approach if these errant cells are indeed the source of raised levels of CyPA. This seems reasonable, but is yet to be proven rigorously. The aging of hematopoietic stem cells takes several forms. The population of functional stem cells declines due to damage, leading to a drop in the number of immune cells produced. This lack of reinforcements is one of the reasons why the aging immune system becomes dysfunctional, cluttered with exhausted, senescent, and malfunctioning cells. In addition, age-related changes in signaling and the stem cell niche in bone marrow cause detrimental changes in the distribution of types of immune cell produced. More myeloid cells and fewer lymphoid cells are produced, a change known as myeloid skew. The aged hematopoietic system promotes hippocampal-dependent cognitive decline In mice and humans, the hematopoiet...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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This study aimed to characterize the role of BDNF in age-related microglial activation. Initially, we found that degrees of microglial activation were especially evident in the substantia nigra (SN) across different brain regions of aged mice. The levels of BDNF and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of BDNF. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of BDNF, while shTrkB...
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We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
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This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
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In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
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This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes. Intron Retention via Alternative Splicing as a Signature of Aging https://www.fightaging.org/archives/2019/03/intron-retention-via-alternative-splicing-as-a-signature-of-aging/ In recent years researchers have inv...
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Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
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In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
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This study cohort is a healthy subset of the EpiPath cohort, excluding all participants with acute or chronic diseases. With a mediation analysis we examined whether CMV titers may account for immunosenescence observed in ELA. In this study, we have shown that ELA is associated with higher levels of T cell senescence in healthy participants. Not only did we find a higher number of senescent cells (CD57+), these cells also expressed higher levels of CD57, a cell surface marker for senescence, and were more cytotoxic in ELA compared to controls. Control participants with high CMV titers showed a higher number of senes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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