Highlights
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Cellular responses to double-stranded DNA breaks erode the epigenetic landscape

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This loss of epigenetic information accelerates the hallmarks of aging

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These changes are reversible by epigenetic reprogramming

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By manipulating the epigenome, aging can be driven forward and backward


Summary
All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called “ICE” (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Link to full text https://www.sciencedirect.com/science/article/pii/S0092867422015707

How America’s ageism hurts, shortens lives of elderly https://link.researcher-app.com/mhCP – via Researcher (@ResearcherApp)

Highlights
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The mitochondrial NAD+ transporter Slc25a51 is a fasting-induced gene.
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Liver Slc25a51 is regulated by circadian rhythm and is a target of BMAL1.
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Reduced Slc25a51 expression suppressed mitochondrial NAD+ levels and SIRT3 activity in hepatocytes and the liver.
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Reduced Slc25a51 expression suppressed oxygen consumption rate in hepatocytes.
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Reduced hepatic Slc25a51 expression caused fatty liver and hypertriglyceridemia in mice

https://www.metabolismjournal.com/article/S0026-0495(22)00153-6/fulltext

The Mitochondrial NAD Kinase Functions as a Major Metabolic Regulator Upon Increased Energy Demand https://link.researcher-app.com/6gAk – via Researcher (@ResearcherApp)

https://pubmed.ncbi.nlm.nih.gov/33783984/

https://medicalxpress.com/news/2022-03-glynac-supplementation-life-span-mice.html

https://pubmed.ncbi.nlm.nih.gov/23043890/

https://www.sciencedirect.com/science/article/pii/S0014579306011458

Summary: Diluting the blood plasma of older mice has a stronger rejuvenating effect on the brain, liver, and muscles than transplanting the blood of younger mice.

Source: UC Berkeley

In 2005, University of California, Berkeley, researchers made the surprising discovery that making conjoined twins out of young and old mice — such that they share blood and organs — can rejuvenate tissues and reverse the signs of aging in the old mice. The finding sparked a flurry of research into whether a youngster’s blood might contain special proteins or molecules that could serve as a “fountain of youth” for mice and humans alike.

But a new study by the same team shows that similar age-reversing effects can be achieved by simply diluting the blood plasma of old mice — no young blood needed.

https://neurosciencenews.com/blood-plasma-aging-16541/

“The accumulation of senescent cells (SnCs) is a causal factor of various age‐related diseases as well as some of the side effects of chemotherapy. Pharmacological elimination of SnCs (senolysis) has the potential to be developed into novel therapeutic strategies to treat these diseases and pathological conditions. Here we show that ubiquitin‐specific peptidase 7 (USP7) is a novel target for senolysis because inhibition of USP7 with an inhibitor or genetic depletion of USP7 by RNA interference induces apoptosis selectively in SnCs. The senolytic activity of USP7 inhibitors is likely attributable in part to the promotion of the human homolog of mouse double minute 2 (MDM2) ubiquitination and degradation by the ubiquitin–proteasome system. This degradation increases the levels of p53, which in turn induces the pro‐apoptotic proteins PUMA, NOXA, and FAS and inhibits the interaction of BCL‐XL and BAK to selectively induce apoptosis in SnCs. Further, we show that treatment with a USP7 inhibitor can effectively eliminate SnCs and suppress the senescence‐associated secretory phenotype (SASP) induced by doxorubicin in mice. These findings suggest that small molecule USP7 inhibitors are novel senolytics that can be exploited to reduce chemotherapy‐induced toxicities and treat age‐related diseases.”

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13117?utm_campaign=RESR_MRKT_Researcher_inbound&af=R&utm_medium=referral&utm_source=researcher_app

Dr. David Sinclair posted this morning on reversing the effects of aging on reproductive viability.

https://www.linkedin.com/posts/sinclairda_our-research-teams-just-published-a-promising-activity-6633781677380423680-fXys

https://www.technologynetworks.com/cell-science/news/reproductive-aging-process-reversed-in-mice-330636

“How energy deprivation induces macroautophagy/autophagy is not fully understood. Here, we show that Atg11, a receptor protein for cargo recognition in selective autophagy, is required for the initiation of glucose starvation-induced autophagy.”

https://www.tandfonline.com/doi/full/10.1080/15548627.2020.1719724?af=R&utm_source=researcher_app&utm_medium=referral&utm_campaign=RESR_MRKT_Researcher_inbound

“The class III histone deacetylase sirtuin 6 (SIRT6) modulates numerous functions in the cell by deacetylating histone lysine residues. Interestingly, SIRT6’s efficiency in in vitro experiments is far greater against substrates carrying long-chain fatty acyl modifications such as myristoylated lysine compared with acetylated counterparts, but the deacetylase activity can be stimulated by fatty acids and small-molecule allosteric modulators. A new study helps to explain this puzzling activation using a novel activator, thorough kinetic investigation, and mutagenesis studies. These data help elucidate the molecular requirements for activation of SIRT6 and provide a foundation for development of activators for therapeutic purposes.”

http://m.jbc.org/content/295/5/1400.full

“The research team has published a new study, which shows that aside from the usual mitochondrial populations living inside our cells, there are also wandering mitochondria floating around in our bloodstreams. From time to time, mitochondria are found outside the cells, but only in the context of debris within platelets, so what are these intrepid mitochondria doing out there alone in the bloodstream?”

https://www.leafscience.org/mitochondria-found-independently-living-in-blood/

“Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor. Rational combinations of these drugs with physical exercise and an anti-aging diet (Koschei formula) can maximize their anti-aging effects and decrease side effects.”

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=18033&path%5B%5D=57761