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Yang et al. demonstrate that inhibition of early-acting autophagy genes in neurons extend C. elegans lifespan, improve neuronal proteostasis and increase exopher formation mediated by the autonomous WD40 domain-related function of ATG-16.2.
Multiple lines of research show that NAD+ has an important role in ovarian aging; however, the role of NAD+ consumption during ovarian aging is incompletely understood. Here the authors study the role of the NADase CD38 to show that CD38 expression increases and NAD+ levels decrease with age in mice, and that CD38 deletion ameliorates ovarian aging.
To analyze neuronal aging in Huntington’s disease, Lee et al. perform direct neuronal reprogramming of longitudinally aged human fibroblasts, uncovering RCAN1 as a therapeutic target to promote neuronal resilience through chromatin reconfiguration.
Stitching together electronic health records with partial longitudinal coverage, Mendelson Cohen et al. use machine learning to untangle healthy aging from chronic disease, identifying markers of healthy aging and analyzing the heritability of longevity.
Using C. elegans, Oleson et al. demonstrate that developmental exposure to reactive oxygen species protects against amyloid toxicity later in life, mediated by disruption of the H3K4me3 epigenetic machinery through HSF-1-dependent shifts in lipid metabolism.
DNA methylation rates correlate with maximum lifespan in mammals, but a precise relationship had not been defined. Here Crofts et al. develop a statistical framework to compare methylation rates at conserved age-related sites and find that methylation rates negatively scale with maximum lifespan in 42 mammalian species.
The authors present the results of a phase 2 study of gosuranemab, a monoclonal antibody targeting N-terminal tau, in patients with early Alzheimer’s disease. Gosuranemab was safe and well tolerated, but the clinical efficacy endpoint was not met.
Partial reprogramming to enhance regeneration and mitigate age-related phenotypes is limited by toxicity. Parras et al. report a transgenic reprogrammable mouse strain with attenuated toxicity, by avoiding OSKM expression in the liver and intestine.
Aging is associated with increased atherosclerosis risk and a changing immune landscape. In this study, the authors examined T cell changes in atherosclerotic plaques in mice with age and report an accumulation of clonally expanded effector and memory CD8+ T cells, including Gzmk+CD8+ T cells, which have cytotoxic transcriptomic signatures.
Aguado et al. show that SARS-CoV-2 induces senescence in human brain organoids and in the brains of COVID-19-infected mice and humans. They demonstrate the therapeutic potential of senolytic therapy in protection against COVID-19-induced brain aging.
Age impacts the effect of dietary health and longevity interventions but the underlying mechanisms are incompletely understood. Here the authors study fasting in killifish and find that older animals exhibit a metabolic shift resembling a fasting-like program, which is counteracted by boosting the activity of AMPKγ1, promoting health and longevity.
Chamoli et al. identified MIC, a benzocoumarin molecule, that promotes longevity in C. elegans by inducing mitophagy via DAF-12/FXR and HLH-30/TFEB, and they demonstrate a conserved MIC efficacy in mammalian cells, indicating potential broader relevance.
There is scant evidence for how intrinsic capacity (IC), the combination of an individual’s physical and mental capacities, varies throughout adulthood. In this study, the authors demonstrated a method to establish IC reference centile curves using data of individuals aged 20–102 years from the French INSPIRE-T cohort.
Using spatial and single-cell multiomics, Nikopoulou et al analyze how different cells within the mouse liver age, revealing zonation-specific aging trajectories and highlighting the importance of the local tissue microenvironment.
Guo et al. demonstrate that oral administration of chiral nanoparticles ameliorates Alzheimer’s disease-associated pathology and cognitive decline in mice via an increase in the gut metabolite, indole-3-acetic acid, potentially a therapeutic target.
Sun et al. identify a stem cell population of CD133+ endothelial-like cells (ELCs) that contribute to neovascularization. ELCs become dysfunctional with age, but ELC supplementation or pamidronate treatment to counter ELC aging promotes longevity.
CREB-regulated transcriptional coactivators (CRTCs) have an important role in modulating transcription in a context-dependent manner. Here the authors dissect the role of CRTC-1 in worm lifespan and show that the CRTC-1 transcriptional domain ensures longevity under specific histone marks.
Change in intercellular communication is an important but poorly characterized hallmark of aging. Here the authors provide a bioinformatics tool to infer changes in cell–cell signaling and an atlas of age-related communication changes in 23 mouse tissues.
Hong, Li and colleagues unveil a pivotal role of TET2 in heterochromatin relocalization, aberrant upregulation of endogenous retroviruses and overactivated innate immune response in hematopoietic stem and progenitor cells during aging.
Advanced age is a primary risk factor for female infertility due to declining oocyte quantity and quality. Here Yu Zhang et al. report that supplementation with spermidine rejuvenates the quality of oocytes from aged mice at least in part by enhancing mitophagy and mitochondrial function.