Cellular senescence is a multi-phenotypic stress or damage response characterized by a stable cell cycle arrest and the secretion of a myriad of biologically active molecules, commonly known as the senescence-associated secretory phenotype (SASP). Thirty years ago, the identification of activated beta-galactosidase during senescence led to one of the first characterizations of senescent cell accumulation during biological aging. Since then, interventions that either selectively eliminate senescent cells or suppress the SASP have demonstrated that they are a major etiological agent for several degenerative pathologies associated with aging. As interest in the development of targeted therapeutics for senescence has grown, so too has the interest in the study of these cells. This has resulted in discovery of new features and phenotypes that often associate with senescence. Here, we review several of these key features of senescence, highlighting the strengths and caveats associated with each.

The inaugural Global Conference on Gerophysics convened 160 researchers across physics, biology, computation, and medicine in Singapore on March 5-6, 2025. With 31 speakers, the two-day event explored how physical laws, and quantitative principles unify aging science, linking biological processes to longevity patterns. Sessions covered diverse aging aspects, from developmental stages to species comparisons. The meeting showcased innovative methods to study aging, emphasizing data-driven insights. A central theme was bridging theory and experiment to advance understanding. It concluded with a consensus around (1) shared multi-modal datasets; (2) physics-based definitions for "aging", "rejuvenation", and "healthspan"; (3) models predicting intervention outcomes; and (4) translational links between non-human species and human research. These priorities outline a practical path for a quantitative, predictive Gerophysics, building on the 2025 conference's insights to shape future aging research.

For decades, research on cellular senescence has predominantly focused on the static identification of senescent cells using markers such as p16 and β-galactosidase, largely overlooking their functional heterogeneity across spatiotemporal dimensions. Accumulating evidence reveals that senescent cells are not merely deleterious pathological byproducts; rather, a subset plays indispensable physiological roles in embryonic development, wound healing, and the maintenance of tissue homeostasis. Based on these insights, this review summarizes the induction mechanisms of cellular senescence and the subsequent evolution of their functional phenotypes across diverse tissues. Consequently, we propose a novel paradigm for senescence management centered on "prevention first, followed by precision intervention." This strategy involves, on one hand, mitigating environmental stressors and optimizing metabolism to intercept the onset of detrimental senescence at its source. On the other hand, it advocates for the functional profiling of existing senescent populations via single-cell omics and lineage tracing, enabling the targeted clearance of "maladaptive" components that drive pathological phenotypes while preserving "beneficial" elements essential for physiological stability. Such a systematic intervention, grounded in the classification of induction factors and functional subtypes, offers a safer and more efficacious trajectory for the prevention of age-related diseases and the extension of healthspan.

Hydra vulgaris ("Hydra") exhibits negligible senescence due to continuous self-renewal and stem cell cycling, contrasting sharply with short-lived, eutelic rotifers that exhibit rapid aging and fixed somatic cell numbers post-development. These organisms therefore represent extremes on the spectrum of invertebrate lifecycles and offer a unique opportunity to test whether patterns of gene expression associated with repressed senescence in Hydra can delay senescence in aging-prone animal models. We hypothesize that introducing Hydra-like gene expression profiles into rotifers (e.g., Brachionus manjavacas) via genetic manipulation will extend healthspan and reduce age-related mortality, providing proof-of-principle for effective manipulation of conserved anti-aging mechanisms. An iterative experimental strategy is proposed, starting with genetic manipulation of key targets in rotifers, followed by validation in Daphnia and mouse models (including strains with enhanced healing or rapid aging). Potential trade-offs, such as neoplasia risk from repressed senescence, will be monitored and mitigated. Data from this approach may identify pathways to inform strategies for delaying aging hallmarks in more complex organisms, including humans. This would assist in the development of appropriate human geroprotective strategies.

Epigenetic clocks of biological aging have been associated with cognitive impairment and dementia. Less is known about whether they are associated with an older-appearing brain or with an atrophy pattern associated with dementia. We examined associations of five epigenetic clocks measured at baseline with the Spatial Pattern of Atrophy for Recognition of Brain Aging (SPARE-BA) and the Alzheimer's Disease Pattern Similarity Score (AD-PS) derived from structural MRIs obtained an average of 8 years later among 1,196 older women. Using linear regression models adjusting for relevant covariates, we observed no associations between any epigenetic clock and accelerated brain aging based on SPARE-BA. We observed a significant association between AgeAccelGrim2 and AD-PS (β = 0.015; 95% CI 0.004 to 0.027; p = 0.01). This association appeared to be primarily driven by the association of a DNA methylation marker of smoking pack years with frontal and temporal lobe volumes. AgeAccelGrim2 was not associated with volumes in regions implicated in early AD (hippocampus and entorhinal cortex). Taken together with prior findings, these results suggest that measures of epigenetic and brain age acceleration capture different aspects of biological aging, and that AgeAccelGrim2 is predictive of neurodegenerative changes associated with smoking that increase risk of dementia.

Progeroid syndromes (PS) are a heterogeneous group of rare hereditary disorders with features resembling premature aging, thereby serving as valuable models for studying human aging biology. However, data on these syndromes remain fragmented across literature sources, with inconsistent terminology and classifications hindering systematic analyses. To address these challenges, we developed a curated catalogue integrating information from 84 publications and the Online Mendelian Inheritance in Man (OMIM) database. This resource consolidates data on 144 genes linked to 56 syndromes and their subtypes, comprising 160 distinct clinical entities, and their associated clinical manifestations categorized into 18 clinical feature groups. The compiled data were visualized and analyzed through a genome-phenome association network, offering new insights into the genetic and phenotypic heterogeneity of these disorders. The gene set was further analyzed through a protein-protein interaction (PPI) network and functional enrichment analysis, revealing a highly interconnected protein network with pronounced enrichment of genome maintenance pathways. Ten highly connected hub genes were prioritized in the PPI network based on degree centrality and further examined in the context of aging by cross-referencing with the Open Genes database, a curated resource of human genes associated with aging and longevity. A case study of the LMNA gene illustrated the pleiotropic impact of single-gene variants across multiple syndromes and related disorders beyond classical PS. Overall, this study provides a reference resource and framework to support future research into premature aging syndromes and their broader implications for understanding physiological aging.

In a randomised controlled trial (RCT), we compared the effects of treatment with furosemide + small volumes of hypertonic saline solution (HSS) with those of furosemide alone in patients with decompensated heart failure (HF), and their effects on inflammatory and remodelling markers and epigenetic signatures. All consecutive patients with acute decompensated heart failure (ADHF) due to heart failure with reduced ejection fraction (HFrEF) were enrolled. Patients were randomly assigned to treatment with i.v. furosemide plus HSS or i.v. furosemide alone. Patients were evaluated at T0 (admission), T1 (after treatment), and T2 (after a saline bolus) to determine serum concentrations of NT-proBNP, hsTnT, s-ST2, galectin-3, IL-6, and CRP and to evaluate some selected miRNA concentrations. We enrolled 200 subjects, 107 randomized to the furosemide plus HSS, and 93 to furosemide alone. At T1, patients treated with high-dose furosemide + HSS had higher absolute delta values of IL-6, hsTnT, NT-proBNP and galectin-3. Patients treated with i.v. furosemide + HSS showed significantly lower increases in the serum concentrations of IL-6, hsTNT, sST2, galectin-3 and NT-proBNP after saline load. We observed a decrease in miR181b expression in subjects treated with i.v. furosemide plus HSS in comparison to patients treated with i.v. furosemide alone and a more significant reduction of miRNA181b expression in subjects treated with furosemide plus HSS. Our findings revealed that in subjects with ADHF, treatment with i.v. furosemide plus HSS significantly decreased the serum levels of IL-6, sST2, hsTnT, galectin-3, and NT-proBNP and modulated some miRNA expression.

While prior research has largely focused on mean Blood Oxygen Level-Dependent (BOLD) activation to understand age-related differences in bimanual coordination, BOLD variability - a metric that captures fluctuations in brain activity -, has been overlooked. Hence, the current study examined how age affects BOLD variability, specifically BOLD standard deviation (BOLD SD), and its modulation with task demands during a bimanual task. Twenty-two younger and twenty-three older adults performed three task conditions of increasing complexity while undergoing functional magnetic resonance imaging (fMRI).Older adults exhibited higher BOLD SD in cerebellar lobule VIIIb and greater modulation across task conditions in both sensorimotor and cerebellar regions. Modulation of BOLD variability predicted task performance in an age- and region-dependent manner: in younger adults, reduced modulation in sensorimotor and visuospatial areas correlated with better performance, whereas in older adults, increased modulation in the inferior and superior parietal lobules was linked to higher performance. Across groups, better outcomes were predicted by greater modulation in the middle occipital gyrus but less in the cerebellar Crus I. These findings underscore an age-related shift in the neural dynamics underpinning motor adaptability with aging, pointing to increased BOLD variability modulation as a potential marker of compensatory reorganization in late adulthood.

Greater adherence to plant-based diets is associated with health benefits. Dietary intake can modify DNA methylation patterns, but it is unknown whether plant-based diets in a largely non-vegetarian population are associated with DNA methylation-based epigenetic aging measures. We examined the associations between 4 different types of plant-based diets indices (PDI) [overall PDI, provegetarian diet, healthy PDI, and unhealthy PDI] and epigenetic aging. We used data from the Atherosclerosis Risk in Communities (ARIC) Study (N=2,810) and National Health and Nutrition Examination Survey (NHANES, N=2,056). PDIs negatively scored higher intake of animal products and positively scored higher intake of all or selected plant foods (overall PDI and provegetarian diet), healthy plant foods (healthy PDI), and unhealthy plant foods (unhealthy PDI). Associations were examined with GrimAge version2, HannumAge, and PhenoAge in each study. Estimates were meta-analyzed using fixed effects model. Each standard deviation (SD) higher in the overall PDI, provegetarian diet, and healthy PDI was associated with decelerated GrimAge2 (range of β = -0.28 to -0.16, P for all tests <0.05). Higher overall PDI and provegetarian diet was associated with decelerated PhenoAge and HannumAge (overall PDI only). No significant association was observed for unhealthy PDI. Following diets rich in plant foods and low in animal products may slow biological aging.