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Heterochronic parabiosis ameliorates age-related diseases in mice, but how it affects epigenetic aging and long-term health was not known. Here, the authors show that in mice exposure to young circulation leads to reduced epigenetic aging, an effect that persists for several months after removing the youthful circulation.
De-Souza, Thompson and Taylor demonstrate that pathogen-associated odorants can activate the UPR cell non-autonomously in C. elegans via neuronal TGF-β signaling, leading to extended lifespan and enhanced clearance of toxic proteins.
Adipose tissue has an important role in metabolic homeostasis and undergoes age-related changes contributing to metabolic decline, via mechanisms that remain incompletely explored. Here the authors show that Crtc2 deficiency in adipocytes protects against age-related hyperactivation of the BCAA–mTORC1 axis and metabolic alterations.
Many age-related disorders, such as neurodegenerative diseases, are associated with protein misfolding. Here, the authors identify LONRF2 as a protein quality control ubiquitin ligase that is expressed in neurons and ubiquitylates misfolded TDP-43 and hnRNP M1 and show that loss of Lonrf2 in mice results in late-onset motor neuron degeneration, whereas its ectopic expression partially rescued the phenotypes observed in motor neurons derived from patients with amyotrophic lateral sclerosis.
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.
Shen, Gao and Luo et al. show that the epigenetic regulator Cxxc1 plays an important role in maintaining homeostasis and function of group 3 innate lymphoid cells that are involved and key in regulating intestinal immunity during aging.
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.
Cognitive dysfunction in aging is a major biomedical challenge without medical therapies. Here, Castner et al. show that longevity factor klotho enhances cognition in aged nonhuman primates, increasing its relevance for a therapeutic path to humans.
Solá, Mereu and colleagues describe a chronic inflammatory state in the aging mouse skin that is characterized by IL-17 production by dermal lymphoid cells and demonstrate the potential of inhibition of IL-17 signaling in protection against skin aging.
Regulatory T (Treg) cells have an important role in age-related diseases and inflammation; however, the underlying mechanisms are not fully understood. Li et al. identify a Treg-specific long noncoding RNA, Altre, that binds Yin Yang 1 to regulate liver Treg mitochondrial function in old mice. Altre deletion accelerates aging-associated liver pathogenesis.
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.
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.
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.
Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.
Oocyte meiotic defects increase with age and contribute to decreased oocyte quality. Here the authors show that granulosa cell mevalonate pathway abnormalities contribute to aneuploidy during ovarian aging and that supplementation with mevalonate metabolites improves oocyte quality, providing a potential therapeutic strategy for promoting female reproductive longevity.
Senolytic compounds have shown promise for the treatment of aging-related diseases in animal models. Here, to discover new small molecule senolytics, Wong, Omori and colleagues introduce a graph neural network platform, identify structurally diverse compounds with favorable drug-like properties and confirm one compound’s in vivo activity in aged mice.
Telomere shortening is a hallmark of aging and genetic telomerase deficiency causes premature aging phenotypes and reduces lifespan. Here the authors show that gut-specific telomerase expression is sufficient to rescue aging phenotypes and extend the lifespan of telomerase-deficient zebrafish, as well as ameliorate signs of aging in wild-type animals.
A mass spectrometric analysis of plasma tau species identifies phosphorylated tau peptides p-tau217, p-tau231 and p-tau205 with distinct correlations with amyloid and tau pathologies and emergences along the AD continuum.