⏳Longevity Signals📈
July 29, 2025
Note: This is not medical advice. Please consult your physician before making changes to your health routine.
🩺 Longevity + Treatments 💪
An AI model stratifies Alzheimer’s patients into subgroups, revealing a robust effect in slow-progressors from a previously failed trial of lanabecestat, a BACE1 inhibitor. The tool achieved 91.1% accuracy, and when applied to a failed clinical trial, it found a 46% slowdown in disease progression with higher drug doses.
Semaglutide, a GLP-1 receptor agonist, has been shown to decrease epigenetic aging in a controlled trial among adults with HIV-associated lipohypertrophy, justifying further evaluation of GLP-1 receptor agonists for health-span extension.
GLP-1 drugs, including Ozempic, have shown promising results in helping people lose weight and reducing risk of various diseases, such as strokes, heart attacks, and cancers. However, the final verdict on these drugs is still pending further research.
Cyclarity Therapeutics’ cyclodextrin-based compound, UDP-003, has shown promising preclinical data suggesting it can reverse foam cell formation in atherosclerosis by removing 7-ketocholesterol (7KC) from cells. This may lead to reducing inflammation, oxidative stress and improving macrophage function. The compound is ready for first-in-human trials.
A structured, higher-intensity lifestyle intervention demonstrated significant improvements in global cognition among older adults at risk of cognitive decline and dementia compared to a self-guided approach. These results suggest that such interventions may be effective in slowing cognitive decline.
A study finds that 7000 daily steps, rather than the commonly recommended 10000, is associated with significant improvements in health outcomes, including lower risks of all-cause mortality, cardiovascular disease, cancer, type 2 diabetes, dementia, depressive symptoms, and falls.
🧬 Longevity + Science 🧪
Researchers have found that epigenetic changes associated with aging, specifically ribosomal DNA (rDNA) methylation and loss of active rDNA, begin after sexual maturity. This insight suggests biological aging may start only after reaching reproductive maturity, and that cells actively maintain youthful rDNA until then.
The article reveals that non-canonical functions of DNMT3A in hematopoietic stem cells help to regulate telomerase activity and maintain genome integrity, potentially enhancing longevity.
An LLM based on health exam records has been used to estimate individual and organ-specific aging using health examination reports has shown promising accuracy. Simple methods like these can often outperform other proxes for future health prediction, although they may offer limited insight into aging biology.
MethAgingDB, a DNA methylation database, has been developed to streamline aging-related epigenetic research and support the development of aging biomarkers. It comprises 93 datasets, 11474 profiles from 13 distinct human tissues, and 1361 profiles from nine distinct mouse tissues.
Long-term obesity in young adults, aged 28 to 31, is associated with accelerated biological aging, evidenced by increased expression of biochemical aging markers.
HIV infection accelerates biological aging in rhesus macaques, with young animals showing greater aging acceleration than older ones. The findings suggest that age and HIV infection interact in complex ways to influence aging progression.
DNA methylation algorithms, particularly GrimAge, show a strong association with cancer risk and mortality in adults over 50, according to a study analyzing data from the National Health and Nutrition Examination Survey.
GrimAge and GrimAge2 Age Acceleration (AA) metrics effectively predict mortality risk, including all-cause, cancer-specific, and cardiac mortality, according to a retrospective cohort study of 1,942 NHANES participants. These epigenetic biomarkers may be valuable tools in ageing-related research.
🧑🤝🧑 Longevity + Teams 📰
This paper outlines 100 critical unanswered questions in the science of ageing, forming a strategic roadmap for anyone interested in extending human healthspan and lifespan. It’s a goldmine for biohackers looking to align their experiments or self-optimization strategies with cutting-edge scientific gaps.
Bryan Johnson, known for his proactive approach towards anti-aging, is considering closing or selling his startup, Blueprint, due to conflicts between running a longevity business and his religion, ‘Don’t Die’. Despite struggles, Johnson asserts that he and the world need Blueprint, and plans to integrate it with ‘Don’t Die’.
This Peter Attia podcast with Brian Kennedy explores a new era of longevity science, including models of aging, human trials on rapamycin, biological clocks, promising compounds and lifestyle interventions.
OpenEvidence, an AI-powered platform that synthesizes peer-reviewed literature for physicians, has secured $210 million in Series B funding. It is seen as a potential tool for longevity medicine, providing real-time, point-of-care guidance and in-depth research support.
Singapore-based longevity investment fund, Immortal Dragons, has launched with $40 million in assets. The fund supports technologies that aim to solve aging and death, investing in areas like xenotransplantation, cryopreservation, regenerative medicine, gene therapies, and 3D bioprinting. It also focuses on infrastructure for the longevity sector and prioritizes impact over economic returns.
90-year-old physicist John Cramer joins an experimental trial testing mitochondrial transplantation for age reversal, developed by biotech startup Mitrix Bio. The project will be overseen by a collaborative team from Stanford, UCLA, Northwell Health New York, and Mitrix Bio.
💡Featured Article 🌟
The study titled “Semaglutide Slows Epigenetic Aging in People with HIV-associated Lipohypertrophy” presents groundbreaking evidence from a randomized controlled trial that semaglutide, a GLP-1 receptor agonist, may slow biological aging. Conducted over 32 weeks, this trial involved adults with HIV-associated lipohypertrophy, a condition linked to accelerated aging due to excessive visceral fat accumulation. The trial’s primary objective was to evaluate semaglutide’s impact on epigenetic aging, using DNA methylation clocks as biomarkers.
Key findings indicate that semaglutide significantly reduced epigenetic aging across several DNA methylation clocks, including PCGrimAge, GrimAge V1 and V2, PhenoAge, and DunedinPACE. These reductions suggest a slower pace of aging and a decrease in biological age, highlighting semaglutide’s potential as a gerotherapeutic agent. Notably, the study found that semaglutide’s effects were most pronounced in second- and third-generation epigenetic clocks, which are predictive of morbidity and mortality risks.
The trial also explored semaglutide’s impact on organ-specific biological aging, utilizing a panel of 11 system clocks. Results showed significant reductions in epigenetic age for systems such as blood, brain, inflammation, heart, kidney, liver, and metabolic domains. These findings suggest that semaglutide’s benefits extend beyond metabolic regulation, potentially influencing multiple physiological systems and contributing to healthspan extension.
For individuals interested in experimenting with treatments that may influence longevity, semaglutide’s demonstrated ability to modulate epigenetic aging markers presents a promising avenue. However, it’s important to note that this study focused on a specific population with HIV-associated lipohypertrophy, and further research is needed to confirm these effects in the general aging population.
