Aging & Longevity

Aging is associated with declining protective immunity and increased autoreactivity, yet the mechanisms linking these processes remain incompletely understood. B lymphocytes are central to this paradox because they integrate antigen recognition, innate signaling, and differentiation under tightly regulated tolerance checkpoints. This review advances the hypothesis that aging appears to drive a progressive, B cell-intrinsic relaxation of central and peripheral tolerance, leading to the...

Mild cognitive impairment (MCI) represents a heterogeneous clinical state where some individuals remain stable while others progress to dementia. Identification of patients who are at high risk for near-term conversion remains a critical challenge for timely intervention. We developed an explainable multimodal machine-learning framework to predict progression from MCI to dementia within a clinically meaningful two-year period. We analyzed 2008 samples from 828 unique MCI subjects from the...

CONCLUSION: Faster gait speed was associated with a lower risk of mortality in adults aged 90 and older. These results were consistent across gender, race/ethnicity, and assistive device use, but differed by age group. Routine gait speed assessment may serve as a simple clinical tool to identify oldest-old adults at higher risk of mortality.

The nuclear hormone receptor NHR-49, a homolog of mammalian PPARα and HNF4α, is a key transcriptional regulator of nutrition sensing and fatty acid metabolism in Caenorhabditis elegans. Here, we examine the role of NHR-49 in reproduction, including oocyte activation and ovulation. Loss of NHR-49 causes inappropriate oocyte activation and laying of unfertilized oocytes in the absence of sperm, resulting in rapid loss of yolk and stored fat, and drastic shortening of lifespan. Conversely,...

Aging and tissue repair involve heterogeneous remodeling across transcriptional, biochemical and cellular dimensions, yet prevailing definitions rely on isolated molecular markers that obscure how these states co-evolve. Here we present RamanOmics, a multimodal framework integrating label-free hyperspectral Raman imaging with single-nucleus RNA sequencing and spatial transcriptomics to link biochemical states with transcriptional programs at single-cell spatial resolution. Applied to young and...

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Bilingualism has been proposed to confer advantages in cognitive aging, yet the neural mechanisms underlying any such advantages remain debated. In a pre-registered analysis of cross-sectional and longitudinal data from elders in the HABS-HD cohort, we asked whether bilingualism is associated with three measures of brain structure (total brain volume, hippocampal volume and white-matter lesions) and/or moderates the relationship between brain structure and two measures of cognition (executive...

Neurodegenerative diseases (NDs) are chronic neurological diseases characterized by progressive neuronal loss and pathological protein deposition in specific brain regions. With the deepening of population aging, these diseases have become one of the most serious public health challenges. Due to the high heterogeneity of these disorders and the complex pathogenesis, it brings great challenges to clinical precision diagnosis and treatment. In this context, nuclear medicine molecular imaging...

Handgrip strength asymmetry (HGSA) and low handgrip strength (LHGS) reflect distinct aspects of muscle health, but their changes over time have been less studied. We examined whether two-wave status patterns of HGSA and LHGS were associated with all-cause mortality in middle-aged and older Chinese adults. We analyzed 8924 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. HGSA and LHGS were assessed in 2011 and 2013 and classified as normal at both waves, newly...

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CONCLUSIONS: In this population-based cohort study, participation in a low-intensity preventive health program delivered in routine care was associated with a lower incidence of diabetes among older adults. However, the observational study design limits evidence on the intervention's role in the observed association, and more robust evidence is needed. Nevertheless, these findings suggest that scalable, population-wide prevention strategies may complement intensive high-risk approaches in...

ObjectivesThis study examines how early-life hardship, wartime exposure, military service, and adult socioeconomic position are associated with grip strength-based possible sarcopenia among older adults in postwar Vietnam.MethodsWe analyzed data from the Wave 1 Vietnam Health and Aging Study among 2,166 adults aged 59 and older. Possible sarcopenia was defined using Asian Working Group for Sarcopenia 2019 grip-strength thresholds; survey-adjusted logistic regression models were...

CONCLUSIONS: Elevated and persistent BNP abnormalities are consistently associated with IC decline, supporting BNP as a practical biomarker for early identification of older adults at risk of functional deterioration.

We aimed to examine the mediating role of accelerated aging in the association between diet quality and CVD incidence and mortality. Data were obtained from the UK Biobank cohort. Diet quality was evaluated using four established indices: the Healthy Eating Index-2020, the Alternative Healthy Eating Index, the Dietary Approaches to Stop Hypertension index, and the Mediterranean Diet Score. Accelerated aging was assessed by the Phenotypic Age Acceleration and Biological Age Acceleration. Outcomes...

Executive and motor function are bidirectionally linked and decline as we age, yet motor-cognitive links are predominantly studied in older adults, while studies focused on midlife report mixed results. We aimed to evaluate whether motor tasks of varying complexity reflect executive function in midlife, a sensitive window for identifying early cognitive-functional risks that are otherwise undetected, thus informing timely intervention strategies. Using a cross-sectional study design, we assessed...

Despite the female predominance in age- and immune-associated diseases, the pathways underlying sex differences in healthy immune aging remain incompletely understood. Here, we analyze a multi-ethnic single-cell transcriptome of healthy human immune aging (35% Asian), comprising 3.8 million peripheral blood mononuclear cells (PBMCs) from 1,828 individuals aged 19-97 years. Prominent peaks of differential gene expression around 40 (mainly CD4 T cells) and after 60 (mainly CD8 T cells) years of...

CONCLUSIONS: Multimorbidity and greater cumulative LTC burden were prospectively associated with incident sarcopenia in both females and males. The graded association across LTC burden and the estimated population-level burden suggest that multimorbidity is an important marker of subsequent sarcopenia risk. Further research should determine whether incorporating muscle health assessment into the care of people with multimorbidity improves prediction or clinical outcomes.

CONCLUSION: Overall, the present study demonstrates for the first time that Nampt activation via P7C3 injections allows for improved fast and slow skeletal muscle function in aged mice with increased muscle quality, myofiber CSA and preserved grip strength.

Traditional vascular aging research has predominantly focused on isolated pathologies in single vascular beds, which fails to explain the synchronized functional decline of multiple organ systems that defines organismal aging. While the panvascular aging paradigm has emerged as a transformative framework for understanding systemic aging, the field remains fragmented by inconsistent phenotypic definitions, arbitrary model selection, and a critical disconnect between basic mechanistic insights and...

BackgroundSubjective cognitive impairment (SCI) predicts Alzheimer's disease and related dementias (ADRD). Identifying SCI correlates may identify cognitive risk earlier in the ADRD continuum. We examined SCI correlates among older non-Hispanic Black (NHB) and non-Hispanic White (NHW) men.MethodCross-sectional data were from 669 men in the 2012 National Health and Aging Trends Study. Logistic regression was used to identify SCI correlates, accounting for complex sampling and...