Volume 2 Issue 7, July 2022

The microenvironment can regulate adult stem cell function during tissue homeostasis and regeneration, but whether and how this is altered in aging is unclear. Ichijo et al. find that increased dermal stiffness, as a result of vasculature atrophy, activates cation channel PIEZO1, leading to interfollicular epidermal stem cell dysregulation.

Muscle function decreases with age, and there are few preventative treatments. Zhang et al. find that different cell types in aging muscle express different senescence markers, giving insight into the complexity of senescence biology. They also show that aspects of muscle aging can be improved with senotherapeutic intervention.

Genetic variation linked to lower levels of soluble ST2, a decoy cytokine receptor for IL-33, may protect against Alzheimer’s disease in women carrying the APOEε4 allele by increasing microglial plaque removal. This discovery advances our understanding of the immune system’s role in Alzheimer’s disease and underscores the importance of sex-specific disease processes.

Global measures of the rate of aging can identify individuals who age faster than average and are at increased risk of adverse outcomes. Combining information on multiple physiological measures collected over time generated a global measure of aging that strongly predicted changes in physical and cognitive function.

Epigenetic clocks based on DNA methylation are widely used aging biomarkers, but their utility is limited by technical noise. A method based on principal component analysis produces high-reliability clocks for applications such as longitudinal studies and intervention trials.

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.

Aging is associated with a decline in stem cell function and impaired tissue homeostasis; however, the mechanisms that lead to the loss of stem cells are incompletely understood. Here the authors show that aging-associated skin vasculature atrophy causes dermal stiffening that leads to epidermal stem cell dysregulation.

Senescent cells accumulate with age and contribute to the functional decline of many tissues; however, their role in skeletal muscle is not well understood. Here the authors comprehensively assess cellular senescence in skeletal muscle of young and old mice and detail senescence features in subpopulations of p16⁺ fibroadipogenic progenitors and p21⁺ myofibers.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Measuring the rate of aging holds potential for capturing heterogeneity in aging. Here, the authors use longitudinal trajectories of aging phenotypes in the Baltimore Longitudinal Study of Aging and create a longitudinal phenotypic score that is associated with accelerated decline in health and physical and cognitive function.

Epigenetic clocks are widely used aging biomarkers, but their utility is limited by technical noise. The authors report a method for producing high-reliability clocks for applications such as longitudinal studies and intervention trials.

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.