Repurposing existing drugs for vascular dementia (VaD) could have clinical impact. Here, using Mendelian randomization, researchers tested whether cholesterol, anti-inflammatory or blood pressure drug targets affect risk of VaD, finding little evidence to support repurposing opportunities. A potential benefit was seen for beta-blocker target ADRB1 while ACE inhibition was observed to potentially increase risk of VaD.

Salladay-Perez and colleagues explore senescence induction in human and mouse macrophages using multiomic profiling. They characterize a p21⁺TREM2⁺ senescent macrophage population, which they functionally implicate in inflammaging and liver disease.

Applying proteomics to longitudinal plasma samples from calorically restricted participants of the CALERIE trial, Mishra, Kim and colleagues link complement protein C3a to inflammaging. In aged mice, visceral fat macrophages produce C3a, and neutralization of C3a blocks inflammaging.

Sopena-Rios and colleagues profile single-cell transcriptomic data from nearly 1,000 female and male participants across the adult lifespan and identify sex-specific changes in inflammation, autoimmunity and disease risk, with more widespread age-related immune remodeling in female participants.

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.

Hartono and colleagues develop an injectable albumin-based nanoprobe to enable urine detection of senescence burden. By exploiting the activity of MMP-7 as a context-specific biomarker of senescence, the probe enables real-time monitoring of treatment response in lung cancer and related pulmonary conditions.

You, Wang, Xu, Zhao, Peng and colleagues identify endothelial cell-derived extracellular vesicles (c-BEEVs) in the cerebrospinal fluid as a potential biomarker for brain vascular pathology and highlight their role in neurovascular dysfunction.

Emerging evidence suggests that organs age at different rates. This study identifies a mechanism by which the naturally hypoxic intervertebral disc ages relatively slowly, via selective autophagy of HIF-1α, and designs a small molecule to export this mechanism across tissues.

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.