Senescence articles from across Nature Portfolio

Skeletal muscle is a highly heterogenous tissue that comprises multiple cell types. Leveraging single-cell and single-nucleus experiments, we systematically mapped the cellular and molecular changes across different skeletal muscle compartments with age. We identify neuromuscular-junction accessory nuclei that may be pivotal in mitigating denervation and uncovered differences between myofiber and myonucleus aging.

The senescence-associated secretory phenotype (SASP) mediates the tissue effects of senescent cells. This Review discusses the composition, regulation and various biological implications of the SASP and its uses as a biomarker and a target of senomorphic drugs to treat cancer and other age-related conditions.

Late-onset hypogonadism (LOH) can occur with male reproductive aging and is characterized by declining testosterone levels as well as other clinical symptoms. Here the authors show that dysregulated phago-/auto-lysosomes in Sertoli cells are a key feature of LOH, linking metabolism and aging, and that pharmaceutical targeting of lysosome dysfunction can alleviate LOH in mice.

Neuroinflammation and microglia significantly contribute to Alzheimer’s disease pathology, depending on their activation state. We found that TREM2-expressing microglia are a heterogenous population spanning activated to senescent cells.

Wu et al. explore vaccine strategies targeting age-related diseases, as well as senescent cells specifically, as potential underlying drivers of aging itself. They discuss challenges faced in clinical trials, as well as further optimizations required to increase therapeutic efficacy.

Skeletal muscle is a highly heterogenous tissue that comprises multiple cell types. Leveraging single-cell and single-nucleus experiments, we systematically mapped the cellular and molecular changes across different skeletal muscle compartments with age. We identify neuromuscular-junction accessory nuclei that may be pivotal in mitigating denervation and uncovered differences between myofiber and myonucleus aging.

After discovering the sensitivity of the adrenal zona reticularis region to aging, we found that low-density lipoprotein receptor (LDLR) deficiency hampers both cholesterol uptake and dehydroepiandrosterone sulfate (DHEA-S) production. This finding reveals the cellular basis for age-related adrenal insufficiency and provides insights for the development of interventions to delay endocrine and systemic aging.

Suda and colleagues explore the enduring consequences of plasma membrane injury in budding yeast and mammalian cells. Their findings highlight that membrane damage induces irreversible cell-cycle arrest and premature cellular senescence, whereas upregulation of plasma membrane repair suppresses them.

Glycerol-3-Phosphate (G3P) and phosphoethanolamine (pEtN) biosynthetic pathways are modulated during senescence establishment to sustain lipid droplet accumulation and senescence-associated secretome. These findings reveal new targets for an immunomodulatory approach against senescent cells.