Aging & Longevity

Physical fitness is a key determinant of health, yet the molecular pathways linking fitness to the risk of aging-related diseases remain unclear. We examined associations between DNA methylation-based protein level estimates (EpiScores) and five fitness traits-VO(2)max, GripStrength, JumpMax, body mass index (BMI), and cognition-in a cohort of 290 mostly old individuals (mean age of 60 ± 11 years). EpiScores for 109 plasma proteins were obtained using the MethylDetectR tool and tested for...

Influenza A virus continues to pose a significant global health burden, with older individuals experiencing disproportionate morbidity and mortality. Although aging is associated with the accumulation of senescent cells, the extent to which cellular senescence contributes to influenza severity remains poorly understood. The aim of this study was to evaluate the therapeutic potential of the senolytic drug ABT-263, a B cell lymphoma-2 inhibitor, in mitigating both acute and chronic damage in an...

The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is...

Accelerated global population aging challenges conventional economic growth paths. Yet, the mechanisms underlying the transition from the age-based demographic dividend, derived from a favorable age support ratio (ASR), to a skill-based dividend, driven by human capital accumulation, remain insufficiently understood. Using population census data for 336 Chinese cities from 2000 to 2020, we develop a task-based skill ratio (TSR) index to quantify the skill composition of local labor markets,...

Human longevity arises from complex genetic and environmental interactions, yet the genetic basis of survival to extreme old age remains underexplored in Asian populations. We performed genome-wide association studies (GWAS) in a Taiwanese cohort, defining survival thresholds at ≥ 85, ≥ 90, and ≥ 95 years, and validated significant loci in an independent cohort. Multiple loci, including ZNF806, NUAK1, TANC1, SLC22A3, PTPRD, and PCSK2, were associated with longevity, of which 14 replicated with...

CONCLUSION: Higher optimism was associated with a lower incidence of dementia. These findings suggest a potential value of optimism in supporting healthy aging, which could be considered in future research on dementia prevention initiatives.

CONCLUSION: Our findings demonstrated OAβT as a reflection of systemic changes linked to early AD pathology. Moreover, the influence of medications and systemic aging on OAβT values pointed to the potential avenues for intervention and emphasized the importance of considering systemic factors in AD pathogenesis and treatment.

Regular physical activity is fundamental in promoting health and longevity. Numerous studies highlight the beneficial effects of exercise on metabolic parameters, but uncovering the mechanisms underlying the complex cellular responses and adaptations remains challenging in humans. Thus, animal models, in particular rodent models, have been indispensable for unveiling the underlying biological responses to exercise. Studies with precise exercise designs and diverse genetic models are vital for...

In the adult brain, hippocampal activity precisely regulates the survival of newborn hippocampal neurons. However, the mechanisms by which these neurons acquire metabolites required for survival remain unclear. Using a genetically encoded glucose biosensor and in vivo imaging in freely moving animals, we tracked cellular glucose dynamics during contextual exploration. Newborn neurons recovered intracellular glucose slowly and expressed low levels of glycolysis- and glucose transport-related...

Male infertility is closely related to DNA double-strand breaks in spermatogonial stem cells (SSCs); however, the precise mechanism still remains to be fully elucidated. While SIRT1 is a key regulator of DNA damage response and cellular senescence in other contexts, its role in SSCs is still poorly understood. In this study, human testicular single-cell RNA sequencing datasets were reanalyzed to characterize SSC transcriptional programs in non-obstructive azoospermia (NOA) patients. Clinical...

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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