senescence
senescence
Overview
Senescence is a stable state of essentially irreversible cell-cycle arrest that cells can enter in response to diverse stresses, including DNA damage, oncogene activation, telomere attrition, oxidative stress, and mitochondrial dysfunction. It is a fundamental biological process with important roles in development, tissue repair, tumor suppression, and organismal ageing. Senescent cells remain metabolically active and often acquire a senescence-associated secretory phenotype (SASP), characterized by secretion of inflammatory cytokines, chemokines, growth factors, and proteases that can alter the tissue microenvironment.
Although senescence can be beneficial in acute contexts such as wound healing and limiting malignant transformation, persistent senescent-cell accumulation is associated with chronic inflammation, impaired regeneration, fibrosis, and age-related disease. In biomedical research, senescence is therefore studied both as a mechanism of ageing and as a potential therapeutic target for geroprotective interventions, including strategies aimed at reducing senescent-cell burden or modulating SASP signaling.
Focus of Latest Publications
Recent publications have examined senescence primarily through the lens of biological aging, using epigenetic clocks, frailty indices, and other aging biomarkers. In a cross-sectional cohort of exceptionally healthy individuals, a saliva-based 9-CpG epigenetic clock was used to assess associations between biological age and supplement or drug use. Delayed-release calcium-alpha-ketoglutarate plus vitamin supplementation was associated with a lower Age Residual, while regular AKG showed a smaller, non-significant effect; coenzyme Q10 and dAKG were associated with lower Age Residual in a longitudinal subset, but these findings did not remain significant after multivariate correction. Another study in UK Biobank and Lifelines linked higher long-term exposure to PM2.5, PM10, and NO2 with accelerated biological aging, and showed that biological aging mediated part of the association between air pollution and mortality or hospitalization.
Other studies extended this aging-focused work to broader determinants of senescence-related phenotypes. A multiomics comparison across ethnicity, geography, and age found ancestry- and geography-related molecular changes affecting metabolism, immune function, microbiome composition, and biological aging, with geography influencing biological age in different directions across populations. A separate study reported that adverse events in childhood and adulthood were associated with molecular, clinical, and functional markers of biological ageing. In a randomized clinical trial, caloric restriction was evaluated for its effects on organ-specific biological aging, reflecting continued interest in interventions that may modify senescence-associated trajectories.
Several publications also connected senescence-related biology with disease contexts and clinical outcomes. A cross-disease microglial transcriptomic analysis spanning aging, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia identified a shared microglial transcriptional program associated with inflammatory and neurodegenerative processes, and highlighted SPP1 as a biomarker of disease-associated microglia states. In oncology, advanced age was associated with higher cancer-specific mortality in bone-only metastatic prostate cancer, and another study examined whether age, comorbidity, and frailty were associated with complications after minimally invasive esophagectomy. Together, these studies show that recent work on senescence has focused on measuring biological aging, identifying environmental and lifestyle modifiers, and linking aging-related biology to disease risk and outcomes.