Wang et al. generate a single nucleus-resolved transcriptomic atlas of primate adrenal aging, with which they demonstrate regional changes in adrenal aging, and establish the role of LDLR in impeding cholesterol uptake and DHEA-S production in aging.

Pan et al. demonstrate that hearing loss promotes cognitive decline in an APP/PS1 mouse model of Alzheimer disease via inhibition of the GDF1 signaling pathway, unveiling GDF1 as a therapeutic target for Alzheimer disease.

Aging is a risk factor of Parkinson’s disease (PD). Adams, Song et al. present a multiomics analysis of the human midbrain showing age-induced changes in genes associated with glial function, with further alterations of oligodendrocytes in PD.

Older age is associated with worse outcomes for patients with melanoma, and the underlying mechanisms are incompletely understood. Here the authors show that the loss of HAPLN1 in aged skin fibroblasts drives melanoma progression by increasing ICAM1 and angiogenesis. Blocking ICAM1 shrinks tumors, suggesting potential for age-specific melanoma therapy.

He et al. characterizes a role of microcephalin (MCPH1), a known regulator of DNA damage response, in hematopoietic stem cell (HSC) aging demonstrating nuclear MCPH1 translocation that leads to activation of necroptosis and deterioration of HSC function with age.

Circulating factors have an important role in aging. Here the authors show that small extracellular vesicles derived from young plasma rejuvenate whole-body physiology in aged mice, at least in part, by stimulating PGC-1α expression and improving mitochondrial energy metabolism.

The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.

Lipid changes across the lifespan and their role in health and longevity are incompletely understood. Here, Tsugawa and colleagues conduct untargeted lipidomics across 13 sample types and four ages in mice, considering sex and microbiome dependencies. This study provides a comprehensive resource of lipid changes with aging and highlights regulatory metabolic components, such as the enzyme UGT8, as potentially responsible for male-specific glycolipid biosynthesis in the kidney.

Aging dynamics of complex lipids are incompletely understood. Here Janssens and colleagues describe lipids that change with age across ten tissues in mice. Notably, bis(monoacylglycerol)phosphate accumulated with age. This lipid also accumulated in muscle of older humans, and reduced upon a short bout of exercise.

Ovarian aging has an important role in health and fertility; however, the molecular mechanisms underlying it remain incompletely understood. Here the authors use single-cell and spatial transcriptomics in reproductively young, middle-aged and older human ovarian tissue to elucidate ovarian aging. They describe spatiotemporal changes in ovarian cells and highlight the important regulatory role of FOXP1.

An inspirational pioneer and leader in the field of cellular senescence.