Aging & Longevity

Aging impairs the function of immune cells and increases susceptibility to diseases such as anxiety and dementia. Nevertheless, some individuals exhibit resilience to age-related impairments, although the mechanisms are still unclear. This study investigated alterations in brain mononuclear cells and their association with age-related behavioral deficits in male and female rats. Flow cytometry was used to analyze the expression of CD45, CX3CR1, and CD163 on brain CD11b+ cells. Aging rats...

The human cortical functional hierarchy, spanning from primary sensorimotor to transmodal association regions, represents a fundamental principle of brain organisation. Here, we show lifespan changes in the sensorimotor-association (S-A) gradient in the cortical functional hierarchy using multimodal neuroimaging data from 33,247 participants aged 32 postmenstrual weeks to 80 years. We identify three critical neurodevelopmental milestones: initiation (third trimester to perinatal period),...

Lactate significantly accumulates in intervertebral disc degeneration (IVDD) to promote inflammation storm and nucleus pulposus cells (NPCs) senescence. However, eliminating the lactate efficiently and inhibiting the inflammation storm and NPCs senescence stimulated by lactate remains a challenge. Here, we show a lactate metabolism reprogramming reactor, which converts lactate to the inhibitor of NPCs senescence (alanine) through orthogonal tandem catalysis (OTC) reaction, thereby guiding the...

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Local radiation injury-induced frailty seriously impacts the quality of life of patients undergoing radiotherapy or nuclear accident casualties and causes a significant medical and economic burden. However, the underlying mechanisms of the frailty remain unknown. In this study, a unique population of hyperactive GAL-9^(high) neutrophils is identified with characteristics of elevated ROS, NETs, and IFN-γ, prolonged lifespan, etc. These neutrophils infiltrate into multiple organs to induce...

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Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic...

CONCLUSIONS: Abdominal obesity control may reduce CVD incidence and mortality, thereby shifting the disease burden toward dementia and FI due to increased longevity, highlighting the need for integrated, life-course public health strategies responsive to the patterns of dementia and its comorbidity in older people.

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In the context of population aging, musculoskeletal fitness has emerged as a cornerstone of overall well-being and injury prevention, relying on the coordinated function of cartilage, bone, and muscle. Drawing on the principle of "increasing income and reducing expenditure," we propose a combinatorial formulation consisting of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide (NMN) and the NAD^(+)-consuming enzyme inhibitor apigenin (API), hereafter referred to as...

This study examined the associations of biological age accelerations (BAAs)-KDM-BA acceleration (via Klemera and Doubal's method) and PhenoAge acceleration (epigenetics-based), defined as residuals from regressing each biological age estimate on chronological age (CA)-with multimorbidity progression (measured by the Charlson Comorbidity Index, CCI), compared to CA. Utilizing UK Biobank data (n = 317,835; median follow-up: 13 years), Cox regression models adjusted for sex, ethnicity, lifestyle,...

CONCLUSIONS: High-load, velocity-intentional resistance training-on land or in water-effectively improves neurocognition, oxidative balance, inflammation, strength, function, and quality of life in older adults. Aquatic training is particularly effective for attenuating oxidative stress and inflammation. Creatine supplementation confers complementary, modality-specific benefits and supports their use in combination to high-speed resistance exercise to promote healthy aging.

Hematopoietic stem cells (HSCs) survive many types of cellular stress but often lose their regenerative and lymphopoietic capacities as a result. Such functional decline also occurs with age, and dysfunctional HSCs with impaired mitochondria accumulate during aging. However, the molecular link between HSC stress response and age-related functional decline remains poorly understood. Here we show that multiple stress responses converge on the RIPK3-MLKL axis to induce age-related changes in HSCs....

Aging is a fundamental biological process that influences cancer development in a context-dependent manner; however, how aging-related programs manifest in hepatocellular carcinoma (HCC) remains incompletely understood. Here, we systematically characterized aging-associated features in HCC by establishing a liver cancer-specific aging signature, termed HCCaging, across more than 2,000 tumor samples from 16 independent cohorts. We comprehensively evaluated its heterogeneity and associations with...

Lumbar spinal stenosis (LSS) affects over 100 million people globally, with an increasing incidence due to an ageing population. While LSS is known to be heritable, its genetic basis remains poorly understood. We conduct a genome-wide meta-analysis of LSS in 40,303 cases and 741,469 controls. We identify 73 previously unreported loci in addition to 15 known loci, and highlight spinal degeneration as a key pathogenic mechanism. In 12,784 surgically treated cases, we discover five loci...

Neuronal intranuclear inclusion disease is caused by abnormal GGC repeat expansion in the NOTCH2NLC gene, though its pathogenic mechanism remains incompletely understood. This study shows that the abnormally expanded polyG-uN2C protein, encoded by the repeat sequence, contains intrinsically disordered regions and forms aggregates, leading to mislocalization of nucleophosmin and downregulation of fibrillarin. PolyG aggregates interact with nucleophosmin and rRNA, disrupting ribosomal homeostasis....

The E3 ubiquitin ligase HUWE1 modifies a diverse network of substrate proteins by ubiquitination, through which it regulates various intracellular processes and contributes to both oncogenic and tumour suppressor mechanisms in different cancer contexts. Here, by analysing human lung adenocarcinoma (LUAD) patient samples, we reveal that HUWE1 protein expression is commonly upregulated in LUAD tumours compared to normal adjacent lung tissue and that this increase is associated with tumour stage....

Malignant tumors are the leading cause of death in individuals over 65 years old, with metastasis as the primary driver. Emerging evidence suggests that age-related metabolic changes and secreted factors increase the risk of metastasis, but the underlying mechanisms remain unclear. Here we demonstrate in mice that extracellular vesicles (EVs) from senescent hepatocytes promote metastasis across tumor types. We show that aged liver tissue exhibits elevated expression of P2X purinoceptor 7...

INTRODUCTION: As the age of the world's population continues to increase it is important to investigate behaviors, such as alcohol consumption, that may negatively impact the health of the older population.