Browse Articles

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.

Skeletal muscle is a highly heterogenous tissue that comprises multiple cell types. Leveraging single-cell and single-nucleus experiments, we systematically mapped the cellular and molecular changes across different skeletal muscle compartments with age. We identify neuromuscular-junction accessory nuclei that may be pivotal in mitigating denervation and uncovered differences between myofiber and myonucleus aging.

Late-onset hypogonadism (LOH) can occur with male reproductive aging and is characterized by declining testosterone levels as well as other clinical symptoms. Here the authors show that dysregulated phago-/auto-lysosomes in Sertoli cells are a key feature of LOH, linking metabolism and aging, and that pharmaceutical targeting of lysosome dysfunction can alleviate LOH in mice.

The advent of plaque-clearing antibodies to the amyloid-β as the first disease-modifying treatment for Alzheimer’s disease will change the course of this disease, the most common type of dementia. Related progress will gradually alter the trajectory of human aging.

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.

Our analysis of the spatiotemporal transcriptional features of human ovarian aging at the single-cell level identified the DNA damage response as a fundamental attribute in oocyte senescence. FOXP1, a gatekeeper both in granulosa and in theca and stroma cellular senescence, can be activated by quercetin treatment to delay ovarian aging.

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.

Wu et al. explore vaccine strategies targeting age-related diseases, as well as senescent cells specifically, as potential underlying drivers of aging itself. They discuss challenges faced in clinical trials, as well as further optimizations required to increase therapeutic efficacy.

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.

Staging Alzheimer’s disease on the basis of the disease’s biological underpinnings might help with stratification and prognostication, both in the clinical setting and in clinical trials. We propose a staging model based on only five biomarkers, which are related to amyloid-β and tau pathologies in different ways and can be measured with a single sample of cerebrospinal fluid.

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.

Xu and colleagues used partial OSKM reprogramming in aged mice to drive cell-type proportions of the subventricular zone to more youthful levels, which equates to qualified rejuvenation of a neurogenic niche that is defined, in part, by restoration of neuroblast levels.

Xu et al. use single-cell transcriptomics to reveal that targeted and systemic partial reprogramming restore the production of neuronal progenitors and new neurons in old mice and show a cell-autonomous effect of reprogramming in cultures of aged neural stem cells.

In a longitudinal population-based cohort, Liu et al. demonstrate that integrating polygenic risk scores and the gut microbiome improved prediction, over traditional risk factors, for heart disease, diabetes, Alzheimer disease and prostate cancer.

Intensive blood pressure control has been suggested to reduce the risk of adverse cardiovascular events. However, the effect of intensive blood pressure control on cardiac conduction system disease has not been clarified. Our study in older patients with hypertension identified no effect of intensive blood pressure control on cardiac conduction system diseases.