⏳Longevity Signals📈
October 21, 2025
Note: This is not medical advice. Please consult your physician before making changes to your health routine.
🩺 Longevity + Treatments 💪
Aging reversal was achieved in old male mice using an Alk5 inhibitor (A5i) and oxytocin (OT), resulting in a 73% life extension and 14% increase in median lifespan, along with improved physical performance, endurance, and memory. The benefits were not seen in female mice, but the treatment had positive effects on their fertility.
MitoQ, a mitochondria-targeted antioxidant, can reduce endothelial cell senescence caused by the chemotherapy drug Doxorubicin (DOXO), by decreasing mitochondrial ROS and DNA damage. This could potentially mitigate chemotherapy-induced cardiovascular toxicity.
Epicatechin, halofuginone, and mitoglitazone have been found to extend lifespan in male genetically heterogeneous mice by approximately 5% and 9% respectively, according to a study by the Interventions Testing Program (ITP). However, these substances did not provide the same benefits to female mice.
Semaglutide, a GLP-1 receptor agonist, may modulate epigenetic age biomarkers, tracking improvements in liver health and physical function in patients with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD).
Glycation-lowering compounds have been found to inhibit ghrelin signaling, resulting in reduced food intake, lower insulin resistance, and extended lifespan. The research offers potential for new treatments in aging and metabolic diseases.
Ergothioneine supplementation improves memory, sleep, liver function and telomere length in older adults, according to a randomized, placebo-controlled trial. While some effects were not sustained, the supplementation was safe and well tolerated.
The FDA has reversed its previous decision excluding Nicotinamide Mononucleotide (NMN) from the definition of a dietary supplement. This move will likely allow NMN to return to market and may impact how future compounds caught between supplement and drug statuses are regulated.
🧬 Longevity + Science 🧪
Researchers identified six genes playing causal roles in aging through a meta-analysis of gene expression datasets and lifespan tests on Caenorhabditis elegans. The direction of differential gene expression with age was found not to predict its effect on lifespan.
Creative experiences across various domains can delay brain aging, enhance brain health and increase connectivity in age-vulnerable brain hubs, according to a study that used machine learning, whole-brain modeling, and Neurosynth metanalyses. High levels of expertise and performance result in greater brain age delay.
New proteomics-based aging clock, ProteAge, reveals distinct aging trajectories for males and females, with females exhibiting more nonlinear changes. ProteAge identifies hundreds of aging rate proteins (ARPs), with only one ARP associated with mortality in females compared to 172 in males.
Cumulative social advantage (CSA), a measure of sustained social connections across familial, religious, emotional, and community domains, is linked to slower epigenetic aging and reduced systemic inflammation, resulting in more favorable biological aging profiles and improved health outcomes.
Sex- and age-specific metabolomic risk scores and MetaboMR clocks improve 10-year mortality prediction beyond traditional models. These clocks and risk scores, underpinned by metabolomics, may assist in personalizing risk stratification in clinical settings.
A study involving the Framingham Heart Study Offspring Cohort has revealed a significant association between 24 out of 43 immune cell phenotypes and 55 out of 68 inflammatory proteins with DNA methylation age metrics. This suggests the potential of immune and inflammatory markers in predicting biological aging outcomes.
The C. elegans dauer stage, a robust and long-lived state, shows a decelerated increase in biological age, and an age reversal upon dauer exit. Major metabolic shifts and enhanced biomolecular degradation are reversed upon exit, providing new insights into naturally occurring age deceleration and rejuvenation.
The article discusses a study on the multi-omic underpinnings of heterogeneous aging across multiple organ systems. The research is important for understanding the variability in how different organ systems age in individuals.
An epigenetic clock, measuring ‘biological age’, is emerging as a novel tool for wildlife conservation. It analyzes patterns of methyl groups in DNA, offering insights into the health and longevity of species. The clock can detect accelerated aging and physiological strain before visible signs of population collapse, potentially providing earlier intervention opportunities.
The review offers insights into the biology of aging in dogs and cats, linking cellular and systemic hallmarks to organ-level pathology and clinical decision-making. It provides veterinarians with tools to improve proactive screening, precision diagnosis, and individualized management in aging pets, potentially extending healthspan and enhancing quality of life.
🧑🤝🧑 Longevity + Teams 📰
The Alliance for Longevity Science, Arts & Entertainment (ALSAE) is a newly launched nonprofit aiming to unite longevity science with arts and entertainment. ALSAE intends to accelerate progress against chronic diseases of aging by targeting root biological processes, and aims to inspire a cultural shift through education.
Stealth BioTherapeutics gained FDA approval for Forzinity, a mitochondria-targeted treatment for Barth syndrome. This is the first regulatory acknowledgment of mitochondrial biology’s therapeutic relevance in human diseases, indicating potential for other therapies targeting similar cellular pathways, including those with healthspan-boosting potential.
Retro Biosciences, co-founded by Joe Betts-Lacroix, uses AI technology to improve cellular reprogramming efficiency. Its four major programs focus on cellular reprogramming, aided by a dedicated AI model based on GPT architecture, which has significantly enhanced the reprogramming process.
AI companies are developing virtual cells to predict healthy and diseased cell functions, accelerating drug development and scientific discoveries. The approach includes visual representation and computer programs for predictions, aided by AI learning directly from cellular data.
Google’s AI DeepMind, in collaboration with Yale University, has generated a novel hypothesis for cancer treatment which has been confirmed experimentally. Their AI model identified a drug, silmitasertib, which could boost immune visibility of ‘cold tumors’ only in certain biological contexts.
💡Featured Article 🌟
The featured article studies nature’s own program for age reversal—the dauer diapause of Caenorhabditis elegans. This unique developmental state, triggered by environmental stress, offers a biological proof of concept for reversible aging. During dauer, nematodes enter a suspended animation that dramatically slows biological aging, preserving cellular integrity and stress resilience. Using the BiT Age transcriptome clock, researchers tracked the molecular age of worms through dauer entry, maintenance, and exit, uncovering a programmed sequence of age deceleration and rejuvenation.
The study reveals that biological age increases far more slowly than chronological time during the dauer stage, then resets sharply upon exit, effectively rejuvenating the organism. Transcriptome-wide analyses highlight extensive metabolic reprogramming and enhanced proteostasis through autophagy and proteasome activation, mechanisms that sustain survival during metabolic suppression. Upon reawakening, these pathways reverse direction, reactivating energy metabolism and cellular biosynthesis. The research also identifies transcription-coupled nucleotide excision repair (TC-NER) as a key process resolving transcription stress caused by DNA lesions, restoring transcriptional integrity as animals resume development.
By demonstrating a naturally evolved rejuvenation cycle, this work is dissecting the molecular architecture of longevity. The findings suggest that the blueprint for age reversal is embedded in development itself, encoded in conserved repair and metabolic circuits. For geroscience and translational medicine, dauer biology offers a tangible roadmap: interventions that boost metabolic efficiency, proteostasis, and DNA repair fidelity may one day mimic the nematode’s natural reset—transforming how we think about halting, and even reversing, the aging process.
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