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We validated AnthropoAge, a biological age (BA) metric, for prediction of mortality and age-related outcomes using harmonized data from the US, England, Mexico, Costa Rica, and China. We estimated AnthropoAge and AnthropoAgeAccel as proxies of BA and age acceleration using body mass index and waist-to-height ratio. We compared mortality prediction of AnthropoAge vs. chronological age (CA) using Cox models and assessed its association with age-related outcomes with generalized estimating...

Heart failure (HF) is a major global and life-threatening disease. Despite advances in therapies, the prevalence of HF is increasing owing to an ageing population and the pervasive pandemic of obesity and metabolic disorders, which have transformed the pathophysiology of HF. Changes in cardiac energy metabolism and the related energy deficit crucially contribute to the severity and type of HF. Furthermore, perturbations in excitation-contraction coupling, mitochondrial function and oxidative...

The number of patients with heart failure is expected to rise sharply owing to ageing populations, poor dietary habits, unhealthy lifestyles and improved survival rates from conditions such as hypertension and myocardial infarction. Heart failure is classified into two main types: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). These forms fundamentally differ, especially in how metabolism is regulated, but they also have shared...

Advances in biomarkers and pathophysiology of vascular contributions to cognitive impairment and dementia (VCID) are expected to bring greater mechanistic insights, more targeted treatments, and potentially disease-modifying therapies. The 2025 Annual Workshop of the Albert Research Institute for White Matter and Cognition, sponsored by the Leo and Anne Albert Charitable Trust since 2015, focused on novel biomarkers for VCID. The meeting highlighted the complexity of dementia, emphasizing that...

In this issue of Neuron, Son et al.¹ reveal how pathologic α-synuclein inhibits autophagy, leading to neurodegeneration. Their work highlights the key roles of the acetyl-CoA-producing enzyme ACLY and aberrant cytoplasmic p300 acetylation, uncovering new therapeutic strategies for Parkinson's disease.

Clusterin (CLU) is a recognized genetic risk factor for Alzheimer's disease. In this issue of Neuron, Lish et al.¹ found that lower CLU levels in astrocytes, caused by the CLU risk allele, heightened inflammation and reduced synaptic functions, potentially increasing risk for cognitive decline.

Saliva is an accessible biofluid with potential for non-invasive disease diagnostics. This study explores how genetic susceptibility to common diseases is reflected in DNA methylation (DNAm) and gene expression profiles in saliva. We constructed cis-mQTL (n = 345) and cis-eQTL (n = 277) datasets and examined correlations between DNAm and gene expression. Saliva QTLs were integrated with summary statistics from 36 genome-wide association studies (GWAS) using Summary-based Mendelian Randomization...

Influenza A virus (IAV) infection causes acute and long-term lung damage. Here, we used immunostaining, genetic, and pharmacological approaches to determine whether IAV-induced cellular senescence causes prolonged alterations in lungs. Mice infected with a sublethal dose of H1N1p2009 exhibited cellular senescence, as evidenced by increased pulmonary expression of p16, p21, β-galactosidase and the DNA damage marker gamma-H2A.X. Cellular senescence began 4 days post-infection (dpi) in the...

Tobacco use is the main source of indoor air pollution and contains a variety of toxic components. The smoke from burning cigarettes is a key environmental risk factor that leads to accelerated aging and the occurrence of numerous diseases. Meanwhile, cigarette smoke and aging are both prominent risk factors for age-related macular degeneration (AMD). This study demonstrates that long-term exposure to cigarette smoke can impair retinal function and induce the aging of retinal pigment epithelium...

Cochlear aging causes substantial hearing impairment in older adults, yet primate-specific mechanisms remain poorly characterized. Our comprehensive analysis combining single-cell and histopathological profiling in aging Macaca fascicularis demonstrates progressive cochlear degeneration featuring accelerated sensory hair cell loss, senescent spiral ganglion neurons with elevated neuroinflammation, and marked stria vascularis atrophy. We discovered that downregulation of transmembrane transport...

Excessive exposure of the skin to UV radiaton (UVR) accelerates the aging process and leads to a photoaging state which involves similar pathological alterations to those occurring in chronological aging. UVR exposure, containing both UVA and UVB radiation, triggers cellular senescence and a chronic inflammatory state in skin. UVR promotes oxidative stress and a leakage of double-stranded DNA (dsDNA) from nuclei and mitochondria into the cytoplasm of keratinocytes and fibroblasts. It is...

Cortical tau deposition begins in higher-order association regions and spreads to lower-order primary sensory-motor networks in moderate/advanced Alzheimer's dementia. The neural mechanisms underlying this spatiotemporal pattern remain elusive. Initial evidence has shown that coupled dynamic, low-frequency (<0.1 Hz) brain activity in cerebrospinal fluid (CSF) flow and gray matter (global brain-CSF coupling) might be related to CSF clearance and thus β-amyloid accumulation. Here, we report that...

Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se...

T stem cell-like memory cells (TSCM cells) are considered to be essential for the maintenance of immune memory. The TSCM population has been shown to have the key properties of a stem cell population: multipotency, self-renewal and clonal longevity. Here we show that no single population has all these stem cell properties, instead the properties are distributed. We show that the human TSCM population consists of two distinct cell subpopulations which can be distinguished by the level of their...

Cellular senescence is an aging-related mechanism characterized by cell cycle arrest, macromolecular alterations, and a senescence-associated secretory phenotype (SASP). Recent preclinical trials established that senolytic drugs, which target survival mechanisms of senescent cells, can effectively intervene in age-related pathologies. In contrast, senomorphic agents inhibiting SASP expression while preserving the survival of senescent cells have received relatively less attention, with potential...

Age is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model. We developed a highly accurate epigenetic...