Reviews & Analysis

Skeletal muscle is a highly heterogenous tissue that comprises multiple cell types. Leveraging single-cell and single-nucleus experiments, we systematically mapped the cellular and molecular changes across different skeletal muscle compartments with age. We identify neuromuscular-junction accessory nuclei that may be pivotal in mitigating denervation and uncovered differences between myofiber and myonucleus aging.

Our analysis of the spatiotemporal transcriptional features of human ovarian aging at the single-cell level identified the DNA damage response as a fundamental attribute in oocyte senescence. FOXP1, a gatekeeper both in granulosa and in theca and stroma cellular senescence, can be activated by quercetin treatment to delay ovarian aging.

Staging Alzheimer’s disease on the basis of the disease’s biological underpinnings might help with stratification and prognostication, both in the clinical setting and in clinical trials. We propose a staging model based on only five biomarkers, which are related to amyloid-β and tau pathologies in different ways and can be measured with a single sample of cerebrospinal fluid.

Intensive blood pressure control has been suggested to reduce the risk of adverse cardiovascular events. However, the effect of intensive blood pressure control on cardiac conduction system disease has not been clarified. Our study in older patients with hypertension identified no effect of intensive blood pressure control on cardiac conduction system diseases.

After discovering the sensitivity of the adrenal zona reticularis region to aging, we found that low-density lipoprotein receptor (LDLR) deficiency hampers both cholesterol uptake and dehydroepiandrosterone sulfate (DHEA-S) production. This finding reveals the cellular basis for age-related adrenal insufficiency and provides insights for the development of interventions to delay endocrine and systemic aging.

Our study demonstrates how clinical data can be used to build machine-learning models to predict the risk of Alzheimer’s disease (AD) onset and can be integrated with knowledge networks to gain insights into the pathophysiology of AD, with a focus on a better understanding of disease sex differences.

Using a data-driven proteomics strategy from a prospective community-based cohort with long-term follow-up, this study reports that plasma levels of glial fibrillary acidic protein (GFAP) can predict the risk of dementia, even 15 years before disease diagnosis. Our findings have important implications for early screening and interventions for dementia.

Using a multi-omics strategy, we uncovered location- and sex-specific aging heterogeneity of the large intestine in monkeys and identified a range of potential gut aging regulators. We explored the roles of several regulators in intestinal function and lifespan in Caenorhabditis elegans. Finally, we investigated potential links between gut aging and colorectal cancer.

Proteomics analysis of cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease (AD) identified five subgroups with distinct underlying mechanisms and genetic risk profiles. These subtypes might be a step forward in realizing personalized treatment for AD.

Tagmentation-based methylation sequencing (TIME-seq) is an efficient and cost-effective solution for measuring and generating epigenetic clocks. We applied TIME-seq to over 2,800 mouse and human DNA samples to produce clocks that demonstrate accuracy and robustness; the method also outperforms conventional methods in speed and cost. The simple and practical design of TIME-seq facilitates large-scale epigenetic clock analysis, which makes it a valuable tool for advancing aging research.