How is it possible to double the lifespan of an organism already close to death? Many biological theories of aging fail to explain this phenomenon. At the Physics of Aging workshop, we used late-life lifespan extension in Caenorhabditis elegans to illustrate how a simple stochastic dynamical-systems model can naturally account for dramatic geriatric interventions. We build on a Langevin-type framework in which aging can occur in stable or unstable dynamical regimes, depending on whether slow, lifespan-determining modes are initially restoring or non-restoring. We argue that C. elegans operates in the unstable regime, a view supported independently by temporal scaling of survival curves, late-life mortality deceleration, and persistent lifespan effects following transient interventions. In the unstable regime, stochastic fluctuations are amplified over time until a failure threshold is reached as a first-passage event. The instability rate α sets the speed of this divergence, while the nonlinear feedback strength g, together with α, sets the failure boundary z_max = α/g. Auxin-induced degradation of DAF-2 in very old animals is interpreted as a late shift in dynamical parameters, and the model naturally accounts for the resulting lifespan extension without requiring reversal of accumulated structural damage. This reconciles persistent senescent pathologies with restored proteostasis and stress resilience, and suggests that altering regulatory instability, rather than reversing damage, can strongly reshape survival trajectories. More broadly, this work illustrates how low-dimensional, physics-inspired stochastic models can capture key features of aging and motivate new collaborations on late-life interventions.

During aging, modifiable lifestyle factors, such as physical activity, play an increasingly important role. Specifically, it is known that physical fitness declines relatively predictably with age and that resistance training can be a highly effective strategy for preventing this decline, both at muscular and cognitive levels. Several studies have described that one of the mechanisms mediating some of the beneficial effects of physical exercise during aging is the regulation of miRNAs, and in particular, the miR-29 family appears to play a relevant role. In this review, we analyse, firstly, the relevance of the miR-29 family in aging and, secondly, the protective effects of resistance exercise in delaying age-related dysfunction through the regulation of miR-29.

Aims: To identify plasma proteins associated with all-cause mortality and determine their relationships with chronic disease burden and biological aging at both the organismal and organ-specific levels, thereby providing insights into the biological mechanisms underlying healthy aging and longevity.

Methods: We conducted a prospective cohort study of 1,025 older adults from the LonGenity study, analyzing 4,265 plasma proteins. Associations between protein levels and all-cause mortality were evaluated using Cox proportional hazards regression over a mean follow-up of 8.05 years. Mortality-associated proteins were further examined for their relationships with chronic disease burden and proteome-derived measures of organismal and organ-specific biological aging. Findings were independently validated in 1,124 participants from the Baltimore Longitudinal Study of Aging (BLSA).

Results: Seventeen plasma proteins were significantly associated with all-cause mortality. Higher levels of Epidermal Growth Factor Receptor (ERBB1) and Anthrax Toxin Receptor 2 (ANTXR2) were associated with lower mortality risk and younger biological age across multiple organ systems. Conversely, higher levels of MIC-1 (GDF15), HE4, and IGFBP-2 were associated with increased mortality and older biological age across multiple organ systems. Specifically, elevated MIC-1 was associated with older organismal biological age, whereas ERBB1 was associated with younger liver biological age. These associations were independently replicated in the BLSA cohort.

Conclusion: Mortality-associated plasma proteins reflect key biological pathways involved in biological aging, physiological homeostasis, and systemic stress. These biomarkers may have potential utility for identifying individuals at increased mortality risk and advancing the development of biomarkers for healthy aging and longevity.

Hibernation is one of nature’s most remarkable examples of reversible physiological adaptation, yet its potential to inform geroscience remains underexplored. Lifespan patterns in hibernators are not fully explained by allometric scaling, as hibernators can outlive non-hibernating species of comparable body size. Hibernation is further characterized by the preservation of tissue function and integrity despite marked calorie restriction, inactivity, and hypometabolism. In this review, we examine the hibernation phenotype as a naturally evolved program of biological maintenance that may limit the accumulation of age-related molecular and cellular damage. We first discuss the relationship between hibernation, longevity, and life-history evolution before reviewing evidence that hibernation modulates multiple hallmarks of ageing through integrated regulation of metabolism, mitochondrial maintenance, proteostasis, nutrient sensing, endocrine signaling, immune function, and epigenetic remodeling. We further highlight emerging observations associating hibernation with telomere maintenance and slower epigenetic ageing, while emphasizing the key knowledge gaps that remain regarding the causal relationship between the phenotype of hibernation and slower ageing, cellular senescence, genome maintenance, and age-dependent changes in hibernation expression. Finally, we discuss how comparative biology, multi-omics approaches, and functional biomarkers of ageing throughout the different phases of hibernation (before torpor, at its onset, during torpor, and after torpor) may help identify evolutionarily conserved protective mechanisms that can be translated into novel strategies to promote healthy human ageing from a bioinspired perspective. This Review was developed following discussions initiated during the September 2025 National Science Foundation (NSF) Quantitative Approaches and Understudied Questions in the Biology of Ageing Workshop (Paris, France).

There is a growing demand from society for gerotherapeutic interventions that can extend healthspan. Yet the increasing commercialization of insufficiently validated gerotherapeutics threatens to undermine the public confidence and the responsible translation of healthy longevity research into practice. The Unlock Healthy Longevity Conference 2026 convened international experts in Singapore to exchange scientific advances in precision geromedicine, with a particular focus on nutraceuticals and repurposed drugs. Precision geromedicine is increasingly being translated into clinical settings; however, standardized frameworks for clinical evaluation, implementation, quality assurance, and oversight remain insufficiently established. This emerging paradigm emphasises the need for collaboration across multiple stakeholders to support the development of a robust, safe, scalable, and equitable ecosystem. A central theme across the sessions was the need to advance clinical human validation, translation, and the development of standards and clinical guidelines. Panel discussions converged on the importance of developing robust clinical and data infrastructures to generate reproducible evidence capable of informing real-world clinical practice and enable equitable access to healthy longevity. Presentations addressed emerging clinical biomarkers of ageing and data-driven approaches to guide gerotherapeutics, including changes in DNA methylation and skin and gut as organ-level readouts of biological ageing. Several potential candidate gerotherapeutics were discussed, including the nutraceutical compounds urolithin A and ergothioneine, and repurposed drugs such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Additional sessions explored the clinical implementation of gerotherapeutics taking into account ethical, safety, and regulatory considerations. This report summarises the key messages and research priorities presented at the conference.