Letters

Research suggests that exercise has a beneficial effect on brain health during aging but more information is needed. Here, the authors show, using UK Biobank data, that the ‘weekend warrior’ physical activity pattern, with concentrated exercise over 1–2 days, is similarly linked to lower risk of brain disorders compared to regular exercise.

Song et al. show that in young mice CD38 supports hematopoietic stem cell (HSC) proliferation by regulating Ca²⁺ signaling and mitochondrial activity. Conversely, the upregulation of CD38 during aging causes dysregulation of NAD metabolism, mitochondrial stress and HSC dysfunction.

Tracking cognitive function over 2.5 years following SARS-CoV-2 infection, Liu, Wu, Wang et al. find that cognitive decline in older COVID-19 survivors in Wuhan, China, manifests primarily in the first year following severe COVID-19.

Gadd et al. identify proteins circulating in the blood that can stratify the risk people have of developing a range of leading age-related diseases, up to a decade before onset.

Using an iterative boost and transplantation model to generate multilifetime T cells, Mi et al. show that cellular epigenetic age can be uncoupled from organism age. While naive T cells appear epigenetically young, memory T cells and T-ALL leukemia can exhibit epigenetic ages exceeding the organismal lifespan.

By analyzing co-evolution of mitochondrial and nuclear genomes across insect species, the authors uncover the evolutionary covariation of a group of non-mitochondrially targeted nuclear genes with mitochondrial genes, including the uncharacterized gene CG11837, which regulates insect lifespan.

Exploring the clonal expansion of somatically mutated hematopoietic stem cells with aging, Mack, Raddatz et al. quantify rates of clonal expansion in 4,370 individuals in the Trans-Omics for Precision Medicine cohort, observing epigenetic and proteomic patterns associated with clonal hematopoiesis of indeterminate potential.

Katsuumi, Shimizu, Suda et al. report that SGLT2 inhibition reduces the senescence burden and alleviates aging traits in mice. The authors demonstrate an indirect mechanism of senescent cell removal, through enhancing immunosurveillance.

The authors developed a proteomic risk score that improved the prediction of hip fractures in three validation cohorts analyzed by two different proteomic platforms. This risk score constitutes a new tool to stratify patients by hip fracture risk.

Cellular senescence is a hallmark of aging but also a potent tissue remodeling process. Here, Nehme et al. show that modulating poly (ADP-ribose) polymerase 1 can switch cell death into senescence, and that inducing senescence improves recovery from kidney ischemia–reperfusion injury.

Bian, Zhang, Guo, Li, Fu et al. present results of a parallel-group, cluster-randomized controlled trial demonstrating the efficacy of an educational intervention targeting college students in increasing COVID-19 booster vaccination uptake among grandparents in China.

In this nationwide administrative register study, individuals diagnosed with infections were three times more likely to be diagnosed with dementia up to 30 years later. Preventing infections might reduce the burden of neurodegenerative conditions.

This study shows that normal microbial exposure increases inflammation and CD8⁺ T cell exhaustion and leads to mortality in old mice; it also shows that anti-PD1 antibody treatment restores survival and increases CD8⁺ cytotoxic capacity, without altering inflammation.

In vivo human neuroimaging shows that locus coeruleus (LC) integrity changes precede medial temporal tau accumulation, and jointly predict future lower cognition in older people at risk for Alzheimer’s disease. A common transcriptomic profile underlies LC’s early vulnerability to tau.

Zhao, Deng and colleagues present a post hoc analysis of the STEP trial showing that intensive blood pressure control does not reduce the risk of cardiac conduction diseases in older adults with hypertension.

An inflammatory profile is associated with aging and senescence. Here, Hao et al. show that TXNRD1 drives the senescence-associated secretory phenotype through the cGAS–STING pathway, independently of its enzymatic activity, during senescence and that the TXNRD1–cGAS interaction may be a target for selectively suppressing inflammaging.

Tijms et al. identify five molecular Alzheimer’s disease subtypes typified by hyperplasticity, impaired immune activation, RNA metabolism, and choroid plexus or blood–brain barrier function. Subtypes may need tailored cures.

Partial reprogramming to enhance regeneration and mitigate age-related phenotypes is limited by toxicity. Parras et al. report a transgenic reprogrammable mouse strain with attenuated toxicity, by avoiding OSKM expression in the liver and intestine.

There is scant evidence for how intrinsic capacity (IC), the combination of an individual’s physical and mental capacities, varies throughout adulthood. In this study, the authors demonstrated a method to establish IC reference centile curves using data of individuals aged 20–102 years from the French INSPIRE-T cohort.

Unlike animals, plants prevent pathological polyQ aggregation through chloroplast proteostasis. Expression of the chloroplast protein SSP in human cell and nematode models prevents disease-related protein aggregation and neurodegeneration.