Aging & Longevity

Intervertebral disc (IVD) degeneration, a major contributor to chronic low back pain, is characterized by the age-related replacement of notochord-derived nucleus pulposus cells (NPCs) with chondrocyte-like or fibrotic cells (CLCs). However, the cellular origins of CLCs and mechanisms driving their emergence remain contentious. Using genetic lineage tracing with Shh-Cre and Gli1-CreER^(T2) to track notochordal and non-notochordal cells, respectively, we demonstrate that CLCs arise from dual...

Ageing is the major risk factor for Alzheimer's disease (AD), the most common neurodegenerative disorder. DNA damage is a hallmark of ageing, particularly when occurring at telomeres, genomic regions vulnerable to oxidative damage and often challenging for the cell to repair. Here, we show that brains of 3xTg-AD mice, an established AD model characterized by amyloid-β (Aβ)-induced pathology, exhibit increased activation of DNA damage response (DDR) pathways at telomeres. Exposure of mouse...

Brain arteriolosclerosis, a prominent small vessel pathology in the aging brain, is associated with cognitive impairment. Understanding the link between arteriolosclerosis and neurodegeneration may be crucial towards unravelling pathways by which arteriosclerosis contributes to cognitive impairment. Using a novel magnetic resonance imaging (MRI) in-vivo classifier for ARTerioloSclerosis termed ARTS, we examined cross-sectional associations between ARTS, cortical thickness, and cognition. Data...

Aging is characterized as a process resulting in the structural and functional deterioration of several essential organs and tissues. This study aimed to determine the effects of normal aging on the cerebellum by using histological and histometric techniques. A total of 24 male Wistar albino rats were divided into three groups: young (4-6 weeks), adult (20-22 weeks), and old (22-24 months). Cerebellar tissue samples were treated using histological and immunohistochemical techniques. The slides...

Objective: To comprehensively evaluate the psychometric properties of the relatively new Everyday Ageism Scale. Methods: Data were from the 2021-2023 Experiences of Aging in Society project (N = 237, ages 50+, multiracial/multiethnic, 72.6% female). We assessed the multidimensional structure, reliability, and validity of the Everyday Ageism Scale. Results: Confirmatory factor analysis generally substantiated the three-factor structure of the Everyday Ageism Scale: exposure to ageist messages,...

Pulmonary Fibrosis (PF) is a life-threatening illness that is characterized by progressive scarring in the lung interstitium. There is an urgent need for new PF therapies because current treatments only slow down the progression of fibrosis, and the median life expectancy post-diagnosis is only 4-6 years. Since PF patients frequently exhibit telomere attrition, overexpressing telomerase, the enzyme responsible for synthesizing telomeres, represents a compelling therapeutic option. In this study,...

Sleep deprivation (SD) and aging are linked to chronic inflammation, a contributor to age-associated diseases. Circadian rhythms, governed by suprachiasmatic nucleus (SCN), regulate immune and inflammatory responses. While aging and SD elevate pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, their impact on temporal dynamics of inflammation across tissues and age groups remains unclear. This study examines age-dependent effects of chronic total SD on daily expression rhythms of...

Finite replicative potential is a defining feature of non-transformed somatic cells, first established by Leonard Hayflick in vitro using WI-38 human lung fibroblasts. Once proliferative capacity is exhausted due to telomere shortening, cells enter into a state called replicative senescence, which can be avoided through ectopic expression of telomerase reverse transcriptase (hTERT). As WI-38 cells approach replicative arrest, molecular pathways linked to mechanotransduction are induced,...

Biochemical and molecular mechanisms associated with testicular aging are still poorly understood. Here, using the Syrian hamster as a natural model of aging, we observed a disturbed spermatogenesis with reduction of the testicular weight and the gonadosomatic index, altered histology including tubular wall fibrosis, increased collagen deposition, and diminished steroidogenesis in testes of aged animals. These changes took place in parallel with an increase in the levels of inflammatory and...

The progressive functional decline associated with aging is a primary risk factor for numerous chronic diseases. The discovery of natural compounds that can modulate conserved longevity pathways offers a promising strategy for promoting healthy aging. Hyperoside, a flavonoid abundant in edible plants such as hawthorn, possesses various pharmacological activities, but its specific role and molecular mechanisms in geroprotection remain poorly understood. This study aimed to elucidate the...

Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were administered in the diet ad libitum beginning at 7 months of age. In male mice, EPI increased median lifespan by ~ 5%, and HAL and MIT each increased median lifespan by ~ 9%. EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents...

Aging leads to neurodegenerative diseases, such as cognitive decline, which are induced by persistent chronic low-grade inflammation in the brain driven by microglial activation. However, whether and how brain-derived exosomes from aged mice (A-exo) induce a pro-inflammatory state and cellular senescence in microglia within the aging brain is poorly understood. Here, we report that brain-derived exosomes from aged mice (A-exo) cause cognitive decline in normal young mice, inducing microglial...

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The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) regulates cell differentiation, proliferation, and function in various tissues, including the liver, adipose tissue, skin, lung, and hematopoietic system. Studies in rats, mice, humans, and chickens have shown that CEBPA mRNA undergoes alternative translation initiation, producing three C/EBPα isoforms. Two of these isoforms act as full-length transcription factors with N-terminal transactivation domains and a C-terminal...

Microglia, the brain's resident immune cells, are crucial for maintaining healthy brain homeostasis. However, as the brain ages, microglia can shift from a neuroprotective to a neurotoxic phenotype, contributing to chronic inflammation and promoting neurodegenerative processes. Despite the importance of understanding microglial aging, there are currently few human in vitro models to study these processes. To address this gap, we have developed a model in which human microglia undergo accelerated...

Cellular senescence is an irreversible form of cell-cycle arrest caused by excessive stress or damage. While various biomarkers of cellular senescence have been proposed, there are currently no universal, stand-alone indicators of this condition. The field largely relies on the combined detection of multiple biomarkers to differentiate senescent cells from non-senescent cells. Here we introduce a new approach: unbiased cell culture selections to identify senescent cell-specific folded DNA...

Rapamycin (RAPA) and related mTOR-inhibitors have been shown to enhance healthy aging in animal models (2-10) and to be generally safe and tolerable in older people (11-13). However, studies to assess their effects on specific age-related pathologies in humans are limited. Since improvements in cardiovascular function with RAPA treatment have been reported in preclinical studies (5, 9, 10, 14-17), we posited that RAPA could be similarly efficacious in humans. Towards this end, we performed a...

Periodontal disease (PD) is a chronic inflammatory condition linked to systemic health issues, yet its relationship with intrinsic capacity (IC)-a key determinant of healthy aging-remained underexplored. The present study investigated the associations between moderate/severe PD and IC domains in older adults in a cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. From the 30,468 NHANES subjects, we included participants aged ≥ 60 years with...

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular...

Alzheimer's disease, a progressive neurodegenerative disorder, is characterized by a decline in brain volume and neuronal loss, with early symptoms often presenting as short-term memory impairment. Automated classification of Alzheimer's disease remains a significant challenge due to inter-patient variability in brain morphology, aging effects, and overlapping anatomical features across different stages. While traditional machine learning techniques, such as Support Vector Machines (SVMs) and...