Aging & Longevity

Memory T cells are maintained in tissues as circulating effector-memory (T(EM)) and tissue-resident (T(RM)) populations for protective immunity, though the role of site and subset in memory persistence remains undefined. Here, we investigated age-associated dynamics of human T cells in lymphoid organs, mucosal sites, and blood over 10 decades of life using retrospective radiocarbon (^(14)C) birth dating, along with cellular, transcriptome, and epigenetic profiling. Memory T cells across...

Idiopathic pulmonary fibrosis (IPF) is a prevalent and deadly age-related disease characterized by chronic, progressive, and irreversible fibrosis. A key effector cell population in the fibroproliferative response is the fibroblasts. Fibroblast cell senescence gradually worsens during aging, and the acquisition of a senescence-associated secretory phenotype (SASP) turns senescent fibroblasts into pro-inflammatory cells. However, the mechanism promoting senescence in IPF, especially at the...

Exercise-induced release of irisin may contribute to the beneficial effects of exercise on brain health. Previous studies in healthy adults have shown ~15 % increase in short-term post-exercise irisin concentrations. However, previous research investigating the exercise-induced release of irisin in older populations is scarce and findings are highly variable. The present study investigated the effects of exercise mode and intensity on short-term acute post-exercise irisin concentrations in older...

Aging is associated with metabolic decline in the brain, increasing susceptibility to neurodegenerative diseases. While exercise is a well-established strategy to counteract these changes, no study has directly compared the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on cortical and hippocampal energy metabolism-key regulators of brain plasticity in aging. To address this gap, we investigated how 4-week MICT and HIIT protocols, structured...

The MYC and RAS oncogenes were found early on to cooperate in the transformation of nonimmortalized primary cells, and in tumor development in transgenic mouse models. MYC prevents RAS-induced senescence. Moreover, tumor regression resulting from the suppression of MYC expression is associated with cellular senescence. How MYC prevents RAS-induced senescence and why suppression of MYC in tumors causes senescence remains to be elucidated. Here, we show that MYC interacts with the Pol β DNA...

The rising prevalence of Alzheimer's disease (AD) due to an aging population has made the search for effective treatments more urgent than ever. Previous studies have demonstrated that continuous ultrasound can depolymerize amyloid proteins, offering potential relief from AD. In this study, we present a portable, fully integrated wearable ultrasound system designed to promote amyloid protein depolymerization. The system comprises a flexible honeycomb ultrasonic array patch, a flexible printed...

Cytomegalovirus (CMV) drives immunosenescence, while its reactivation is associated with inflammation and oxidative stress. This study investigates the interplay between CMV, oxidative stress and inflammation in a cohort of 2065 age-stratified individuals randomly recruited from the general population (RASIG), as part of the MARK-AGE study, to better understand the role of CMV in immunosenescence and its potential impact on age-related diseases. CMV IgG titers were associated with oxidative...

CONCLUSION: Higher levels of handgrip strength showed a lower risk of developing AD, among adults aged 50 years and over. However, the dose-response relationship is limited to specific ranges according to age group. We identified a range between 54 and 56 kg years and a range between 31 and 49 kg as suitable to prevent AD in adults aged 50-64 and ≥ 65 years, respectively. Routine assessment of hand grip strength can help healthcare professionals identify people at increased risk of AD....

CONCLUSIONS: Population ageing is a dominant driver of the growing global stroke burden, necessitating targeted public health interventions for ageing populations.

CONCLUSIONS: Replacing SB with walking and improving neighborhood accessibility were significantly associated with reduced risk of being pre-frail or frail. These findings highlight the importance of considering these factors when designing age-friendly environments for older adults.

The common, late onset form of Alzheimer's disease (AD) selectively impacts higher brain circuits, with tau pathology and neurodegeneration preferentially afflicting glutamatergic neurons in the limbic and association cortices. Understanding this selective vulnerability may help reveal the etiology of sporadic AD and therapeutic targets for prevention. The current review describes that these vulnerable circuits express magnified calcium signaling needed for higher cognition and memory, but that...

CONCLUSION: This study highlights the importance of managing depression and optimizing sleep duration in addressing the risk of cognitive decline in older adults with hypertension.

Alzheimer's disease and related disorders (ADRD), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one data set can be pursued using different analytical techniques, each with different assumptions or purposes. Whereas a great deal of research has explored clustering individuals of variables that exhibit greater similarity in some way, little research has explored evidence for...

ER and mitochondrial stress are often interconnected and considered major contributors to aging as well as neurodegeneration. Coordinated induction of ER^(UPR) and mito^(UPR) has been observed in diabetes and pulmonary disorders. However, in the context of aging and neurodegeneration, regulation of this intra-organellar crosstalk has remained relatively elusive. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial protein, accumulates at the ER-mitochondrial contact...

Mosaic loss of chromosome Y (mLOY) is the most common somatic mutation in hematopoietic cells of aging men and is linked to cancer risk and mortality. However, its relationship with treatment modalities remains unclear. In 348 prostate cancer patients at Juntendo University Hospital, local radiotherapy was associated with a higher prevalence of mLOY (OR = 2.55, 95% CI: 1.08-6.50, P = 0.04), whereas surgery and endocrine therapy were not. We then examined BioBank Japan data from over 30,000...

Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design synthetic catalytic condensates that selectively recruit enzymes to investigate this temporal evolution. We show that catalytic condensates exhibit time-dependent activity: they initially accelerate enzymatic...

Physiological brain aging is associated with cognitive impairment and neuroanatomical changes. Brain age prediction of routine clinical 2D brain MRI scans were understudied and often unsuccessful. We developed a novel brain age prediction framework for clinical 2D T1-weighted MRI scans using a deep learning-based model trained with research grade 3D MRI scans mostly from publicly available datasets (N = 8681; age = 51.76 ± 21.74). Our model showed accurate and fast brain age prediction on...

The accumulation of amyloid fibrils has been identified in tissues outside the brain, yet little is understood about the formation of extracerebral amyloidosis and its impact on organ aging. Here, we demonstrate that both transgenic Alzheimer's disease (AD) mice and naturally aging mice exhibit accumulated senescent bone marrow adipocytes (BMAds), accompanied by amyloid deposits. Senescent BMAds acquire a secretory phenotype, markedly increasing secretion of serum amyloid P component (SAP), also...

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CONCLUSION: This qualitative study provides new insight into the dilemma of subsequent fragility fracture prevention among elderly individuals. Starting from cultural concepts and proactive health education, helping the elderly establish a positive attitude toward aging can enhance their awareness of subsequent fracture prevention and treatment, as well as their initiative and confidence in health management. Meanwhile, perpetuating the beneficial effects of Confucian culture and enhancing...