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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.
Cipriano et al. review recent progress in using epigenetic reprogramming to combat age-related deterioration at the cellular, tissue and organismal level, discussing reprogramming strategies and mechanisms, as well as remaining challenges in the field.
This Perspective describes and discusses the Information Theory of Aging, which proposes that aging primarily stems from the loss of youthful epigenetic information that can be restored via epigenetic reprogramming to heal injury and reverse aging.
China faces urgent challenges associated with population aging. In this Comment, we summarize China’s adoption of long-term care insurance and underscore its importance for social and economic wellbeing. We provide recommendations for a future of sustainable and healthy aging in China.
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.
Preclinical models are central to aging research. Yet, these models often lack key features of female humans. Here, the authors discuss shortcomings in the study of female aging and share opportunities for closing the gap in our understanding of sex-dependent aging trajectories.
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.
Targeting tau in addition to amyloid-β could be the next phase of disease modification in Alzheimer’s disease. The TANGO trial of gosuranemab, which binds the tau N terminus, affected neither clinical outcomes nor brain levels of aggregated tau. The results highlight the importance and challenge of reducing aggregated tau.
In vivo reprogramming by expression of the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM factors) has been associated with early mortality and cancer. We report that these adverse effects are associated with liver and intestinal dysfunction. Strategic control of OSKM expression in these organs through a newly developed transgenic mouse model reduced adverse effects. Our model yields valuable insights into the potential of in vivo reprogramming for rejuvenation and regeneration.
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.