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Our understanding of the genetics that underlies healthy aging can be improved by integrating complementary traits related to chronological and biological aging. We present a multitrait genome-wide association study that reflects the genetics of a broad healthy aging factor and use genetics methods to investigate potential therapeutic relationships among various drug targets.
By applying deep molecular profiling to our long-term mouse parabiosis model, we reveal reduced epigenetic age in old mice that shared circulation with young mice. The rejuvenation effect is sustained at two months after detachment, leading to lifespan extension and improved physical function, and is associated with rejuvenated transcriptomic signatures.
Han et al. provide a substantial contribution to our limited comprehension of the mechanisms of aging in adipose tissue. They show that, with age, increased levels of adipose CRTC2 decrease the breakdown of branched-chain amino acids and activate mTORC1. This in turn leads to increased levels of senescence-associated secretory phenotype factors, which promotes senescence and adipose dysfunction.
Neuronal aging is highly associated with misfolded protein aggregates that predispose to neurodegeneration, but the cellular factors that are involved in removing misfolded proteins are yet to be identified. In this issue of Nature Aging, Li and colleagues identified LONRF2 as an important player in protecting aging neurons against the accumulation of protein aggregates.
We treated aged monkeys with a dose of the longevity factor klotho, which is known to increase synaptic and cognitive functions in mice. We found that a relatively low dose of klotho enhanced cognition in aged monkeys. These findings are important because they suggest that klotho replenishment could prove to be therapeutic in aging humans.
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.
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.
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.
High-throughput analysis of cellular landscapes is an important tool to decipher the molecular mechanisms driving aging and disease. Here, Singh and Benayoun discuss key considerations in the design and analysis of omic data to gain robust and reproducible insights into the aging process.
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.
Li and colleagues address the effect of regulatory T (Treg) cells on the aging process and the role of long non-coding RNAs in Treg cell function. They show that a Treg cell-specific and age-induced long non-coding RNA, Altre, protects the aging liver from age-related apoptosis and metabolic abnormalities.
Liu and colleagues investigate the effects that ovarian aging may have in granulosa cell-to-oocyte communication and demonstrate that oocyte rejuvenation and the extension of reproductive lifespan is possible by increasing lipid metabolism in granulosa cells in mouse.
Quantification of tau peptides in blood samples using a new mass spectrometry method suggests that individual phosphorylated tau peptides have distinct patterns of emergence in Alzheimer’s disease and differential associations with amyloid and tau pathologies. This method has the potential to stage patients along the disease continuum and for clinical trials.
This Perspective describes the clinical relevance of animal models in dementia for translational research. The authors emphasize incorporating aging as a component in model organisms to understand its contribution to disease pathogenesis.
This Review provides an update on the most promising blood-based biomarkers relevant to Alzheimer’s disease and how they can be used to substantially improve the diagnostic and prognostic work-up in clinical practice and trials.
This Review provides evidence-based update on the association between social interaction and risk of dementia. The authors propose a policy framework to promote social interaction as a preventative strategy against dementia.
This Review highlights the need for targeting Alzheimer’s disease in the preclinical stage for an effective therapeutic strategy. The authors provide an update on candidate therapies in development, current preclinical Alzheimer’s disease trials, recruitment challenges and future directions.
This Perspective outlines a strategy to move towards a future with personalized medicine for Alzheimer’s disease by empowering patients in orchestrating diagnosis, prediction and prevention of the onset of dementia.
We used graph neural networks trained on experimental data to identify senolytic compounds from vast chemical libraries of over 800,000 compounds and discovered structurally diverse senolytics that have potent in vitro and in vivo activity, as well as favorable medicinal chemistry properties.
Lamming and Mannick discuss work over the past decade showing that rapamycin promotes survival in multiple species and how recent clinical trials have finally begun to explore whether existing mTOR inhibitors can safely prevent, delay or treat multiple diseases of aging in humans.