Aging & Longevity

Microglia are brain-resident immune cells with complex physiological functions. Exploring their proteomic heterogeneity at the single-cell level has remained technically challenging. Here, we optimized a label-free single-cell proteomics (SCP) workflow using Orbitrap Astral mass spectrometry (MS) and applied it to fluorescence-activated cell sorting (FACS)-sorted microglia from the hippocampus and prefrontal cortex of young, middle-aged, and aged mice. This yielded one of the largest SCP...

Cellular senescence is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential. Circulating senescence signatures are predictive of age-related traits and diseases, though cell type senescence signatures have not been comprehensively explored. In this study, senescence signatures from the Senescence Catalog (SenCat), including 14 human cell types are examined in circulation for clinical relevance in two longitudinal...

There is an urgent need to comprehensively catalog senescence markers across cell types in an organism in order to characterize senescent-cell heterogeneity. Here, we profiled the transcriptomes and proteomes in 14 different primary human cell types undergoing over 30 senescence paradigms to create a senescence catalog we termed "SenCat." We found that while senescent cells from all primary cell types did not share a single unique marker, they did activate shared specific metabolic and...

No abstract

White matter hyperintensities (WMHs) are increasingly recognized as neuroimaging biomarkers of cerebrovascular pathology in Alzheimer's disease (AD), yet their temporal relationship with amyloid and tau accumulation remains unclear. While previous studies suggest bidirectional associations between WMHs and AD pathology, regional associations between WMHs and AD pathology have yet to be examined. This study investigated the temporal and regional associations between PET measures of amyloid (Aβ)...

Similarities and differences in the self-assembly of actin filaments from different species inform our understanding of its evolution. However, this basic knowledge is largely incomplete. Here, we systematically characterize assembly kinetics for actin from two yeast species that are five hundred million years apart in evolution, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and compare them to the well-studied rabbit muscle actin from which they diverged a billion years ago. We find...

CONCLUSION: Awareness of age-related losses may be adaptive when it reflects realistic recognition of age-related challenges, like hearing difficulties. Promoting positive, gain-focused views of aging could support earlier informal help-seeking among older adults by encouraging open conversations about hearing concerns within their close social networks.

Cancer and cell-aging studies may have relied on antibodies to incorrect molecule.

Labor is mediated proximately by prostaglandin signaling within gestational tissues and must be tightly regulated for birth to occur after appropriate fetal development. Metabolic changes accompanying gestational aging have been postulated as a determinant of birth timing, but specific nutrients, sensors, and messengers remain obscure. We report that placental nicotinamide adenine dinucleotide (NAD^(+)) dynamically tunes gestational length. Depletion of placental NAD^(+) in mice provoked labor...

CONCLUSIONS: The findings suggest that limited uptake of digital elder care is closely tied to moral legitimacy and ethical recognition. Digital care services are more likely to be accepted when perceived as a supportive extension of, rather than a replacement for, family care responsibilities. Addressing ethical lag through culturally resonant service design and trusted community mediation may help reduce inequalities in engagement and improve the effectiveness of ageing-related service...

A decline in nuclear factor erythroid 2-related factor 2 (NFE2L2)-orchestrated adaptive homeostasis and oxidative distress are thought to be key features of aging. In contracting skeletal muscle, the reactive oxygen species-producing enzyme NADPH oxidase 4 (NOX4) is a potent inducer of NFE2L2 adaptive homeostasis. Here, we report that skeletal muscle NOX4 levels decline in aged mice and humans, resulting in abrogated NFE2L2 adaptive homeostasis, increased protein oxidative damage, and decreased...

Growing energy demands and renewable integration are stressing the aging power grid infrastructure. Lignocellulosic oil-impregnated paper is widely used in power transformers but suffers from critical limitations, such as low dielectric strength, mechanical strength, and thermal conductivity, causing premature transformer failures. Here, we demonstrate a superior electrically insulating oil-impregnated paper design using the naturally anisotropic structure of densified wood veneer to achieve...

CONCLUSION: While rural Veterans were less likely to use HCBS overall, there was substantial variability across facilities. These findings demonstrate that some VAMCs counteract the overall trend by ensuring rural Veterans receive HCBS at rates comparable to urban Veterans.

Establishment of the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier requires precise coordination between diverse cell types to protect and nourish the brain. Here, we identify developmentally programmed p21^(+) senescent cells that exhibit divergent senescence-associated features across these two brain interfaces in mice. In the choroid plexus (ChP), epithelial cells adopt a lifelong, non-inflammatory senescent state associated with CSF production and blood-CSF barrier...

Aging emerges from nonlinear interactions among primary, antagonistic, and integrative hallmarks that progressively erode tissue resilience. As global demographics shift and chronic disease burden intensifies, extending healthspan with mechanistic precision has become imperative, accelerating the incorporation of artificial intelligence into geroscience. AI leverages multi-omics, spatial biology, imaging, and clinical data to reveal nonlinear structures linking hallmark interactions to tissue...

Alzheimer's disease (AD), characterized by progressive cognitive decline, represents a major public health challenge in aging societies. Since the proposal of the amyloid cascade hypothesis, Aβ-targeted therapeutic strategies have dominated this field for over three decades. Although recent anti-Aβ antibodies have shown modest promise, their limited clinical benefits coupled with safety concerns underscore the necessity of re-evaluating the pathological mechanisms underlying AD. Cerebral...

Muscle regenerative capacity declines with aging and disease, which leads to muscle loss and reduced lifespan. Muscle regenerative failure is related to a disrupted network orchestrated by multiple muscle-harbored cell types; whether and how the interplay between macrophages and myofibers contributes to this process is largely unknown. Herein, we report upregulation of histone methyltransferase G9a in both aged human muscle and mouse muscle after injury. Deletion of G9a in either myeloid cells...

Cancer-related lymphedema (CRL) is an incurable disease characterized by progressive swelling of extremities. One of the risk factors in developing CRL is cancer treatments, including surgery and radiation. This leads to damage to the lymphatic system, causing accumulation of interstitial fluid, infiltration of inflammatory cells and cytokine release, tissue remodeling, accumulation of subcutaneous fat, and fibrosis. Radiation therapy (RT) inhibits lymphatic proliferation and survival by...

Identifying biomarkers that identify vulnerability to age-related cognitive decline is a major priority in aging research. Adropin, a circulating peptide that regulates metabolic and vascular homeostasis, has been associated with cognitive performance in humans, but its relevance across species has remained unclear. Here we report low plasma adropin concentrations associate with poor decision-making in aged rhesus macaques subject to an increasing food choice test paradigm. Animals with higher...

Nanoparticle sintering is typically regarded as a deactivation mechanism for supported metal catalysts, motivating efforts to maximize metal dispersion. Here we demonstrate the opposite trend for platinum catalysts in light-alkane oxidation. Intentionally pre-sintered platinum particles, tens of nanometers in size and supported on thermally stable magnesium aluminate, show higher activity than highly dispersed platinum species for propane oxidation. Theory-guided adsorption calculations suggest...