⏳Longevity Signals📈
December 16, 2025
Note: This is not medical advice. Please consult your physician before making changes to your health routine.
🩺 Longevity + Treatments 💪
Engineered virus-like particles (VLPs) have shown promise in in vivo gene editing of human hematopoietic stem and progenitor cells (HSPCs), a key to treating various hematological diseases. Two different VLP envelopes demonstrate efficient transduction of HSPCs, with one achieving higher in vivo specificity.
Anti-uPAR CAR T cells can improve gut function and inflammation, and enhance tissue regeneration in aged mice by targeting aging-related uPAR-positive cells, suggesting a potential immune-based cell therapy for aging-related disorders.
CBL-514, a small-molecule injectable drug, significantly reduced abdominal subcutaneous fat volume with a favorable safety profile, offering a noninvasive treatment alternative for effective targeted fat reduction.
GLP-1R agonism shows potential in counteracting aging across the body, according to a study published in Cell Metabolism.
Athlete-derived extracellular vesicles (AEVs) can protect against spinal cord injury by inhibiting neuronal ferroptosis, a type of cell death. AEVs deliver RNF216, which promotes degradation of NOX1, reducing ferroptotic damage and enhancing recovery. RNF216-enriched vesicles also improve synaptic plasticity, supporting neuronal regeneration.
Theobromine, a dietary alkaloid from cocoa, is associated with reduced epigenetic age acceleration, suggesting its beneficial effects on health and ageing extends to the molecular epigenetic level in humans.
🧬 Longevity + Science 🧪
NRF1, a nuclear respiratory factor, drives inflammaging through innate immune responses and contributes to cellular senescence. NRF1 deficiency can delay senescence and improve age-related organ deterioration. Targeting NRF1 could present a potential avenue for treating inflammaging.
A platform called ClockBase Agent uses AI agents to comb through millions of human and mouse methylation and RNA-seq samples alongside over 40 aging clock predictions, identifying over 500 interventions that significantly reduce biological age.
The article suggests that longevity in species may evolve under constraints presented by the need to reduce cancer risk. Mechanisms that suppress cancer, such as telomere shortening and cellular senescence, may inadvertently promote ageing by limiting cell proliferation and tissue regeneration.
Melanocyte stem cells (McSCs) undergo senescence-coupled differentiation in response to DNA double-strand breaks, leading to hair greying and protection against melanoma. Carcinogens can suppress this process, even with double-strand breaks present, promoting McSC self-renewal.
Pregnancy accelerates within-person epigenetic aging by up to 5.3 years. Older first-trimester epigenetic age, but not chronological age, is associated with pregnancy complications, suggesting that gestation may influence biological aging and epigenetic age could be a potential marker of pregnancy health.
Sterilization and contraception methods are associated with increased lifespan in mammals, with evidence of improved survival in males limited to castration. Complementary meta-analyses show improved survival with sterilization across vertebrates and increased healthspan in gonadectomized rodents.
Aging-associated DNA methylation drift, which is linked to cancer, originates within intestinal stem cells and is driven by inflammation and reduced Wnt signalling, leading to dysregulated iron metabolism and impaired TET activity.
A methodological appraisal of the DrugAge database revealed significant shortcomings in the reporting of preclinical anti-aging studies. Only one third of non-mammal findings translated to mammals, and there was a large variation in reporting quality and effects across species.
🧑🤝🧑 Longevity + Teams 📰
The 1st World Longevity Summit in Japan highlighted the need for global collaboration towards healthy aging strategies. The report emphasizes the importance of bonds with communication, dietary fiber, physical activity, and a sense of purpose for healthy aging. A presentation on epigenetic clocks revealed they could be key tools for understanding biological aging dynamics.
San Francisco tech startup Medra is developing a ‘physical AI’ platform for drug discovery, aiming to accelerate research into aging and age-related diseases. The platform uses AI to generate hypotheses and robotic execution in the lab for continuous experimentation, addressing issues in drug R&D.
Pharmaceutical company AbbVie has ended its collaboration with Calico Labs, the Alphabet-backed biotech focused on aging and age-related diseases. Despite significant investment, the partnership yielded limited clinical success, leading to a shift in AbbVie’s focus towards biologics and advanced modalities.
Harvard professor George Church is focusing on Lila Sciences, a startup aiming to build a ‘Scientific Superintelligence’. The company uses AI models and large robotic labs to test hypotheses and generate proprietary data, which could revolutionize scientific research.
Pharma giant GSK is shifting its focus to preventive medicine to improve healthspan with an emphasis on data and analytics. Despite challenges, Chair Sir Jonathan Symonds is optimistic about using current advances in computing power and analytics to understand human biology and disease prevention.
💡Featured Article 🌟
The article “Reporting quality, effect sizes, and biases for aging interventions: a methodological appraisal of the DrugAge database” published in npj Aging, examines the quality of preclinical studies on anti-aging interventions using the DrugAge database. This database compiles studies on various interventions aimed at extending lifespan in non-human animals. The authors, Austin Parish et al., conducted a comprehensive analysis of 667 studies to assess the quality of reporting, methodological rigor, effect sizes, and potential biases.
Key findings highlight significant deficiencies in the reporting of critical study design features such as randomization and blinding. Only 19.9% of studies mentioned randomization, and a mere 4% reported blinding of interventions, indicating a lack of methodological rigor. The study also found that the translation of findings from non-mammalian species to mammals was limited, with only one-third of results applicable to mammals, suggesting challenges in the applicability of these studies to human health.
The analysis revealed that most interventions were initiated early in the organism’s lifespan, which may not accurately reflect potential benefits when applied later in life, a crucial consideration for human applications. The median sample size was 200 animals, but there was a wide variation in study designs and species used, which could affect the generalizability of results.
For individuals interested in experimenting with longevity treatments, these findings underscore the importance of critically evaluating the methodological quality of preclinical studies. The lack of rigorous study designs and the limited translation of results to mammals suggest that caution should be exercised when interpreting the potential efficacy of anti-aging interventions based on animal models.
The study calls for improved reporting standards and methodological rigor in preclinical research to enhance the reliability and applicability of findings to human health. This is particularly important given the growing interest in interventions that target the aging process, which could potentially offer broader health benefits than treatments targeting specific diseases. The authors advocate for more robust experimental designs and transparent reporting to facilitate the development of effective anti-aging therapies.
🍫Cocoa slows aging, 👶Pregnancy ages mom, 🏃♂️Athlete EVs heal
Longevity Signals ⏳Longevity Signals📈 December 16, 2025 Welcome to Longevity Signals, a briefing brought to you by the Clock Foundation. Each week, we hunt for
🧠 Multilingualism delays aging, 🕰️ Horvath clocks lead, 🧬 NR’s weak effects
Longevity Signals ⏳Longevity Signals📈 November 18th, 2025 Welcome to Longevity Signals, a briefing brought to you by the Clock Foundation. Each week, we hunt for
🐭❤️ Oxytocin combo extends life, 💊 NMN returns, 🐛 Dauer decoded
Longevity Signals ⏳Longevity Signals📈 October 21, 2025 Welcome to Longevity Signals, a briefing brought to you by the Clock Foundation. Each week, we hunt for