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Category: life extension – Page 91
Key Enzyme Found to Drive Inflammation in Aging Cells
The research focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging.
This cellular state, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.
Frontiers: To date, the most studied drug in anti-aging research is the mTOR inhibitor – rapamycin
Despite its almost perfect anti-aging profile, rapamycin exerts one significant limitation – inappropriate physicochemical properties. Therefore, we have decided to utilize virtual high-throughput screening and fragment-based design in search of novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Seven lead compounds were selected from the list of obtained hits that were commercially available (4, 5, and 7) or their synthesis was feasible (1, 2, 3, and 6) and evaluated in vitro and subsequently in vivo. Of all these substances, only compound 3 demonstrated a significant cytotoxic, senolytic, and senomorphic effect on normal and cancerous cells. Further, it has been confirmed that compound 3 is a direct mTORC1 inhibitor. Last but not least, compound 3 was found to exhibit anti-SASP activity concurrently being relatively safe within the test of in vivo tolerability. All these outstanding results highlight compound 3 as a scaffold worthy of further investigation.
GRAPHICAL ABSTRACT
Anti-Aging Enthusiasts are Taking this Pill to Extend Their Lives?
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Key Protein Regulates DNA Enzymes, Supporting Genome Stability
Summary: Researchers have discovered that the protein USP50 regulates DNA replication by managing which enzymes—nucleases or helicases—cleave or unwind DNA strands during replication. This control is crucial for stable replication, especially when the process encounters issues that need restarting. When USP50 is absent, cells struggle to coordinate enzyme use, leading to replication errors and potential genetic instability.
The findings provide new insights into genome maintenance and may help explain some hereditary conditions, such as early-onset aging and certain cancers. Understanding USP50’s role opens doors to potential therapeutic strategies aimed at protecting DNA integrity.
Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
To support the data generated in Il11ra1-deleted mice on a mixed C57BL6/129 genetic background30 and to more deeply dissect age-related effects, we studied young (3-month-old) and aged (2-year-old) female mice with deletion of Il11 (Il11−/−) on a C57BL6/J background31.
Immunoblots confirmed IL-11 up-regulation across tissues in old age in this additional strain (Fig. 1m). Old female Il11−/− mice had lower body weights and fat mass and preserved lean mass (Fig. 2a–c). The frailty score15 of old female Il11−/− mice was lower than that of old wild-type mice and their body temperatures were mildly increased (Fig. 2d and Extended Data Fig. 5a). Lower frailty scores were largely driven by improvements in tremor, loss of fur colour, gait disorders and vestibular disturbance (Supplementary Table 1). Muscle strength was higher in both young and old Il11−/− mice (a phenomenon that was observed for some other phenotypes) compared with age-matched controls (Fig. 2e and Extended Data Fig. 5b).
Chronic inhibition of mTORC1 with rapamycin can cause glucose intolerance owing to indirect inhibition of mTORC235. It was therefore important to more fully assess the effects of IL-11 inhibition on liver function, metabolism and glucose utilization in old mice. As wild-type mice aged, there were increases in serum AST, ALT, cholesterol and triglycerides, which were collectively mitigated in old Il11−/− mice (Fig. 2f and Extended Data Fig. 5c, d). Glucose tolerance test (GTT) and insulin tolerance test (ITT) profiles of old Il11−/− mice were similar to those of young wild-type mice, whereas GTTs and ITTs of old wild-type mice showed impairment (Fig. 2g and Extended Data Fig. 5e, f). Indexed skeletal muscle mass was greater in both young and old Il11−/− mice compared with the equivalent wild-type mice (Extended Data Fig. 5g).
Tech Millionaire Bryan Johnson Claims His “Super Plasma” Reversed His Father’s Age By 25 Years
Bryan Johnson, a millionaire tech entrepreneur dedicated to reversing ageing, recently took to social media to boast about his “super clean plasma.” In a detailed post on X, he shared that a lab technician couldn’t bring himself to dispose of the plasma after a total plasma exchange (TPE) procedure.
Johnson claims to have reduced his epigenetic age through his comprehensive regimen called Project Blueprint. He follows a strict diet and exercise routine, spends over $2 million annually on a team of doctors and medical equipment, and undergoes both experimental and conventional treatments-including the recent TPE procedure.
TPE, a procedure often used in regenerative medicine and anti-ageing treatments, involves replacing a patient’s plasma with donor plasma or a substitute fluid. In Johnson’s case, his plasma was replaced with albumin.
Dr. Mehmood Khan, MD — CEO, Hevolution Foundation — Expanding Healthy Human Lifespan for All
Expanding Healthy Human Lifespan for All — Dr. Mehmood Khan, MD — CEO, Hevolution Foundation.
Dr. Mehmood Khan, MD is the Chief Executive Officer of Hevolution Foundation (https://www.hevolution.com/), a first of its kind non-profit organization that funds research through grants and provides investments in biotech to incentivize healthspan science across disciplines and borders for the benefit of all. Established by a Saudi Royal Decree, with its headquarters in Riyadh, with additional international hubs to support the expansion and execute the global mission, it’s vision is to expand healthy human lifespan for the benefit of all humanity.
Hevolution Foundation aims to be positioned as a global leader, catalyst, partner, and convener, to increase the number of scientists entering the field, to increase the investable opportunities in the field of aging, and to help shape the regulatory and government environment.
Dr. Khan also currently serves as the Executive Chairman of Life Biosciences Inc. where he joined the company in April 2019 as the Chief Executive Officer and Board Member. Life Biosciences was founded to advance scientific research and develop innovative new therapies to improve and extend healthy lives for everyone.
Dr. Khan previously served as Vice Chairman and Chief Scientific Officer of Global Research and Development at PepsiCo, a Fortune 50 company employing upwards of 250,000 employees across 22 brands. At PepsiCo, Dr. Khan played a pivotal role in the company’s global R\&D efforts to create breakthrough innovations in food, beverages, and nutrition, including the incorporation of healthier and more nutritious offerings across its portfolio. Dr. Khan also oversaw PepsiCo’s global sustainability initiatives based on the belief that success in business is inextricably linked to the sustainability of the world we share.
