Volume 3 Issue 7, July 2023

Li and colleagues address the effect of regulatory T (T_reg) cells on the aging process and the role of long non-coding RNAs in T_reg cell function. They show that a T_reg cell-specific and age-induced long non-coding RNA, Altre, protects the aging liver from age-related apoptosis and metabolic abnormalities.

Aging increases vulnerability to respiratory viral infections, including by SARS-CoV-2. Delval et al. established a causal role for age-related pre-existing senescent cells in the severity of COVID-19 symptoms in an aging hamster model. Selective depletion of senescent cells using senolytic agents mitigated the risk of severe COVID-19 symptoms linked to aging.

Warde and colleagues demonstrate sex-specific differences in senescence in the adrenal glands of aged mice, with males eliciting a more robust, protective myeloid response that is associated with protection from adrenal cancer.

Aging is associated with a variety of changes; however, which of the observed changes drive aging is incompletely understood. In this Perspective, the authors discuss cellular senescence, epigenetics and stem cell alterations with this question in mind.

SenNet Consortium members review current and emerging methodologies for spatially resolved mapping of senescent cells. They discuss their limitations and challenges involved in the aim of creating a comprehensive atlas of senescent cells during aging.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

Regulatory T (T_reg) cells have an important role in age-related diseases and inflammation; however, the underlying mechanisms are not fully understood. Li et al. identify a T_reg-specific long noncoding RNA, Altre, that binds Yin Yang 1 to regulate liver T_reg mitochondrial function in old mice. Altre deletion accelerates aging-associated liver pathogenesis.

Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.

The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens.

Yeo and Zhou et al. profile whole-genome chromatin accessibility in different cell types of the adult neurogenic niche, which reveals a reversible decrease in the migration of proliferative neural stem cells in aged mice.

Microglia, the innate immune cells of the brain, exhibit diverse functions and can influence Alzheimer’s disease progression. This study explores human microglial diversity in Alzheimer’s disease, uncovering unique disease-associated microglial populations and predicting underlying gene regulatory networks.