Sharma and colleagues show that, in Caenorhabditis elegans, age-associated decline in peroxisomal function causally impairs lipid mobilization, resulting in lipid droplet accumulation, metabolic inflexibility and secondary mitochondrial dysfunction. Restoring peroxisomal activity reinstates metabolic resilience during aging.

A parsimonious model of stem cell dynamics describes how DNA methylation changes arise and propagate with age, unifying diverse epigenetic aging patterns and suggesting that stem cell dynamics are a key driver of aging across mammals.

The authors developed a multitask deep learning framework integrating domain knowledge with large pretrained models that effectively predicts Alzheimer’s disease diagnosis, cognitive scores and future cognitive decline using only baseline MRI and demographics.

Apolipoprotein E (APOE) is the strongest genetic influence in Alzheimer’s disease (AD). Compared to the most frequent allele, ε3, the ε4 allele increases AD risk, and the ε2 allele is protective. Here, in a multicohort proteomic study, the authors show that APOE ε2 and ε4 are linked to distinct early protein signatures before amyloid pathology, helping explain why they have opposite effects on AD risk.

Sharma and colleagues show that, in Caenorhabditis elegans, age-associated decline in peroxisomal function causally impairs lipid mobilization, resulting in lipid droplet accumulation, metabolic inflexibility and secondary mitochondrial dysfunction. Restoring peroxisomal activity reinstates metabolic resilience during aging.

A parsimonious model of stem cell dynamics describes how DNA methylation changes arise and propagate with age, unifying diverse epigenetic aging patterns and suggesting that stem cell dynamics are a key driver of aging across mammals.

The authors developed a multitask deep learning framework integrating domain knowledge with large pretrained models that effectively predicts Alzheimer’s disease diagnosis, cognitive scores and future cognitive decline using only baseline MRI and demographics.

Apolipoprotein E (APOE) is the strongest genetic influence in Alzheimer’s disease (AD). Compared to the most frequent allele, ε3, the ε4 allele increases AD risk, and the ε2 allele is protective. Here, in a multicohort proteomic study, the authors show that APOE ε2 and ε4 are linked to distinct early protein signatures before amyloid pathology, helping explain why they have opposite effects on AD risk.

Autophagic activity has a protective role in Alzheimer’s disease in mice. Here the authors investigate the role of autophagy-initiating protein ULK1 and report that its overexpression stimulates autophagic flux, reduces amyloid and tau pathology and delays cognitive decline.

The authors investigated metabolic remodeling in response to stem cell activation and the effect of aging on this response. Aging muscle stem cells lose a key glutamine-fueled metabolic pathway that powers de novo lipogenesis needed for activation. This study shows that reductive TCA cycling helps preserve stem cell function and may offer a new target against sarcopenia.

Observation-induced behavioral changes can produce biomarker shifts comparable to or exceeding those of the tested interventions. This phenomenon, known as the Hawthorne effect, is especially pronounced in geroscience trials. This Comment proposes a methodological framework to distinguish true biological aging modulation from the confounding effects of study participation.

Emerging evidence suggests that extracellular matrix (ECM) states can shape both senescence entry and persistence by tuning integrin signaling and mechanosensing. We propose a self-reinforcing circuit that contributes to age-related senescent cell accumulation, in which age-associated ECM remodeling favors senescence and senescent cells further remodel the ECM to amplify dysfunctional tissue niches.