Understanding sex differential responses to geroprotective interventions is key to developing personalized longevity treatments. Here, Regan, Lu et al. show that the sexual identity of intestinal enterocytes regulates autophagy to determine the response to the drug rapamycin.

A new population of dysfunctional astrocytes in the aging mouse hippocampus called autophagy-dysregulated astrocytes (APDAs) show impaired protein homeostasis and defective regulation of synapse formation and elimination and appear early in a mouse model of Alzheimer’s disease.

The hypothalamus controls homeostatic functions such as metabolism and sleep, which undergo age-related changes. Here the authors perform single-nuclei transcriptomics profiling of young and old hypothalamus from female mice and describe changes in gene expression with age, in particular increased expression of the X inactivation gene Xist.

The authors discuss how adopting a complex systems perspective is a crucial step in advancing our understanding of the aging process and requires fundamental alteration of the questions being asked and the methods used to answer them.

Sen et al. show that, during human cellular senescence and mouse tissue aging, chromatin alterations promote the initiation of transcription from non-canonical sites and lead to deterioration of cellular health.

By showing that the immune modulator MANF is induced after muscle injury in young but not aged mice and is essential for regenerative success, this study reveals a new link between immune dysfunction and regenerative decline in muscle aging.

Xiao et al. report a weaker adaptive immune response in older adults after inactivated SARS-CoV-2 vaccination compared to young adult controls, identifying altered immune cell function and decreased antigen-specific receptor repertoire diversity as potential underlying mechanisms.

Cerebrospinal fluid (CSF) tests are used in the clinical diagnosis of Alzheimer’s disease. This study found that CSF tau phosphorylation at two sites (T217 and T205) is a better test for Alzheimer’s disease pathology than currently available tests.

Single-cell transcriptomic profiling of young and old mouse brains following heterochronic parabiosis shows regulation of several canonical hallmarks of aging by a shift in age-induced changes of the transcriptome in a cell-type-specific manner.

By applying quantitative chemical cross-linking technologies, the authors show that changes in the mitochondrial interactome of the skeletal muscle contribute to mitochondrial functional decline in female mice.