Aging & Longevity
Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders
Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in...
Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging
The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC)...
Higher openness and conscientiousness are associated with lower risk of long-term care needs: A 22-year follow-up of community-dwelling older adults in Japan
CONCLUSION: Among older adults living in the community, higher openness and conscientiousness were protective against future LTC needs. These findings highlight the potential role of psychological traits in promoting autonomy and healthy aging.
CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models,...
Silencing lipid catabolism determines longevity in response to fasting
Oscillations between lipid anabolism and catabolism are essential for maintaining cellular health during metabolic fluctuations. Fasting, a conserved determinant of aging, improves disease outcomes and extends lifespan, yet the relative contributions of lipid catabolism versus its attenuation to fasting-induced longevity remain unresolved. The metabolic flexibility of C. elegans under variable nutrient availability provides a powerful system to address this question. We show that lifespan...
Single-cell atlas of human lung aging identifies cell type dyssynchrony and increased transcriptional entropy
Age is a major risk factor for lung disease. We characterized the changing cellular, transcriptional, and genomic landscape of human lung aging using single-cell RNA sequencing. We find that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest transcriptional changes. Among alveolar epithelial cells, aging is associated with a decreased relative proportion of surfactant-expressing SPC^(high) AT2 cells. Among alveolar capillary cells, we...
DNA methylation-based surrogate markers of C-reactive protein and their associations with health-related traits
Several methylation-based surrogate markers of C-reactive protein (mCRP) have been proposed and used to assess the risk of age-related phenotypes and construct novel ageing markers. We aimed to (i) assess the variance in plasma CRP explained by several mCRP markers; (ii) compare their associations with three health-related traits: mortality, body mass index (BMI), and PCGrimAge; and (iii) assess the stability of CRP and mCRP over a decade. Blood samples were collected from 947 participants in...
Targeting age-related LINE-1 activation alleviates cardiac aging
Cardiac aging is a major driver of cardiovascular diseases and associated mortality, yet its therapeutic options are limited. While long interspersed nuclear element-1 (LINE-1) retrotransposons are known to drive cellular senescence, their role in cardiac aging is poorly defined. Here we showed that LINE-1 expression increased in the heart with age. To investigate their role in cardiac aging, we generated cardiomyocyte-specific Mov10-knockout mice, which failed to suppress LINE-1. These mice...
Molecular damage associated with ageing drives inflammation in cardiovascular disease
Chronic inflammation has long been recognized as a major risk factor for and a causal contributor to cardiovascular disease (CVD). However, advances in omics technologies and deepening insights into CVD pathogenesis have expanded our understanding of the underlying mechanisms. Inflammation is now seen not as an isolated cause, but as one of several biological responses to cumulative tissue damage over time. In this Review, we propose that inflammation initially functions as a resilience...
SARC-F and six modified versions: prognostic role for prolonged hospital stay and 1-year mortality in older inpatients
CONCLUSION: Our study demonstrates that all SARC-F-based approaches are linked to prolonged LOS, and almost all approaches were also linked to 1-year mortality. We also introduce the novel (BMI-adjusted) SARC-CalF + MUAC version, pending future validation.
EFFECT OF A NEW PHYTOCOMPASSION ON THE CONTRACTILE ACTIVITY OF LYMPH NODES IN OLD ANIMALS
CONCLUSION: Phytocorrection proved to be effective in stabilizing the structural components of the lymph nodes, which maintained their contractile function at an adequate level. The composition is a geroprotector, and the biologically active substances in the phytocomposition correct and stimulate the lymph nodes' own transport function. Activation of the contractile activity of the lymph nodes is an important link in the body's anti-aging. This phytocorrection may have a wider application.
Myelin is repaired by constitutive differentiation of oligodendrocyte progenitors
Oligodendrocytes form myelin sheaths around axons to enable rapid signaling within neural circuits. The generation of new oligodendrocytes through differentiation of oligodendrocyte precursor cells (OPCs) promotes myelin plasticity and repair in the adult brain. Here, we performed genetic interrogation and in vivo analysis of OPCs in the mouse brain to determine their differentiation dynamics. Our results show that OPCs attempt to differentiate throughout the adult central nervous system with...
Addressing the Aging Workforce Crisis Through Intergenerational Programming: A Retrospective Analysis of Perfect Pair
CONCLUSION: Perfect Pair encourages and prepares college students to pursue a career in aging and engages them in issues associated with aging. This has strong implications for future intergenerational programming that aims to promote workforce development in the aging space.
Lactucopicrin promotes the autophagic degradation of MAP2K4/MKK4 by mediating CCDC50 palmitoylation to alleviate osteoarthritis progression
Macroautophagy/autophagy plays a crucial role in maintaining cellular homeostasis and protecting against osteoarthritis (OA). Its dysregulation contributes to OA progression by promoting chondrocyte senescence, inflammation, and cartilage degradation. Enhancing autophagic activity thus represents a promising therapeutic strategy for OA. In this study, we identified lactucopicrin (LCP) as an effective autophagy activator that alleviates OA progression in a mouse model induced by the...
Follicle-stimulating hormone linked to cognitive decline and amyloid burden in postmenopausal women
INTRODUCTION: Women have a higher risk of developing Alzheimer's disease (AD) than men, with hormonal changes during menopause being a potential factor. However, the exact relationship between these hormonal changes, cognitive function, and AD pathology is not fully understood. This study investigates the differential associations between serum follicle-stimulating hormone (FSH) and estradiol levels with cognitive function and cerebral amyloid-βeta (Aβ) deposition, quantified using amyloid...
Impact of the 2015 Dutch Long-Term Care Reform on Nursing Home Use and Access for People With Dementia
CONCLUSION: Among older Dutch people with dementia, the 2015 Dutch LTC reform was associated with fewer NH admissions and longer waiting lists. While stabilization of the NH admissions may reflect prioritization of persons with dementia within stricter eligibility criteria, the concurrent rise in waiting list prevalence suggests that institutional capacity did not keep pace with persistent need. As a result, many older people with dementia remain longer in the community, raising concerns...
Concurrent associations between visit-to-visit changes in actigraphy-based physical activity and cognitive aging in older adults
Physical activity (PA) is associated with lower dementia risk, yet few studies examine objectively measured PA with concurrently measured brain and cognitive aging outcomes longitudinally, leaving a gap in knowledge regarding temporality of these brain-behavior associations. We examined how longitudinal within-person changes in average daily step count track with changes in memory, executive function, hippocampal volumes, white matter hyperintensities (WMH), and depressive symptoms over time....
Longitudinal body mass index exposure-based threshold to prevent mortality for populations with type 2 diabetes mellitus
The long-term body mass index (BMI) threshold to prevent mortality among aging individuals with type 2 diabetes mellitus (T2DM) remains unclear. We quantify BMI exposure using two metrics: the percentage of time BMI above target range (TAR) and the percentage of time BMI within target range (TTR). In a cohort of 3,708 adults aged ≥40 years with T2DM and at least 5 BMI measurements across 4 years, 1,020 deaths occurred during a median 5-year follow-up. Sustained BMI ≥27 kg/m² (TAR) is positively...
Evaluating Senescence-Targeted Approaches in Alzheimer's Disease: What We Know and What Lies Ahead
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, which represents the most prevalent dementia worldwide. Although amyloid-β (Aβ) and tau pathology have been the classic focus of treatment, accumulating evidence indicates that ageing-associated cellular senescence plays a central role in AD pathogenesis. Senescent neurons, astrocytes, microglia and endothelial cells accumulate in the ageing and Alzheimer's brain and adopt a senescence-associated secretory...
Corrigendum to "Inhibitor PF-04691502 works as a senolytic to regulate cellular senescence" [Exp. Gerontol. 186 (2024) 112359]
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Aging and Longevity: Latest results from PubMed
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