Aging & Longevity

No abstract

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by pronounced clinical and molecular heterogeneity, as well as highly interconnected pathogenic pathways. This biological complexity has long hindered efforts to systematically define disease mechanisms and to develop effective, targeted therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) based functional...

Cellular senescence exerts powerful non-cell autonomous effects through the senescence-associated secretory phenotype (SASP). This SASP comprises soluble factors and extracellular vesicles (EVs). Although soluble SASP components can induce senescence in neighboring cells, the specific contribution of EVs to paracrine senescence is poorly defined. Here, we show that EVs released by senescent tumor cells are necessary and sufficient to propagate senescence. Conditioned media from bleomycin-induced...

Thymic involution, the age-related replacement of thymic soft tissue by fat, has been linked to immunosenescence and chronic inflammation, processes implicated in aging-associated comorbidities. Untreated HIV infection is associated with thymic atrophy and reduced thymic output. Although thymic function may normalize after initiation of antiretroviral therapy, the long-term consequences of HIV infection on thymic involution in people with HIV (PWH) remain unknown. We investigated whether thymic...

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and...

Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr^(-/-) mice with established atherosclerotic...

Age-related weakness is strongly associated with disability and mortality in older adults. While muscle atrophy contributes to weakness, strength declines at a faster rate than muscle mass, implicating neural mechanisms such as changes at the spinal cord and neuromuscular junction. Yet, the role of the motor cortex in age-related weakness remains largely unexplored. We previously identified layer V pyramidal neurons (LVPNs) of the primary motor cortex as hyperexcitable in aged mice, but whether...

Mitochondrial quality control is severely impaired in the aging heart, largely attributed to disrupted mitophagy homeostasis. However, the key molecular drivers remain poorly defined, and the translational value of mitochondria-targeted therapy for cardiac aging is still underexplored. Here, we report prominent mitophagy flux congestion in aged cardiac tissue and confirm that mitochondrial transplantation efficiently rescues impaired mitophagy, ultimately rejuvenating the aging heart....

The gut microbiota plays a pivotal role in maintaining intestinal homeostasis and regulating host metabolism, yet its composition and function undergo substantial alterations with aging. However, the relationship between age-associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or...

Aging is often associated with intestinal microbiota imbalance and immune system degeneration. The dysregulation and crosstalk of these two factors markedly elevate the elderly's susceptibility to infections and age-related diseases. Polygonatum odoratum, a traditional Chinese medicinal herb, is widely used in geriatric care for its lung-moistening and nourishing effects. However, its potential regulatory roles on the microbiota and immunity in the aging context remain unreported. A total of 140...

Skeletal ageing involves changes in endocrine regulation, mechanical loading and cellular function that can impair bone remodelling. Cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as mechanisms that help close this gap. In the ageing bone microenvironment, senescent osteocytes, mesenchymal stem cells, osteoblasts, immune cells, and vascular endothelial cells secrete pro-inflammatory cytokines, chemokines, matrix metalloproteinases, and Wnt antagonists...

Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated with menopause and its links to brain aging. In n = 80 rigorously staged (STRAW+10) pre-, peri- and postmenopausal women (aged 43-58 years) with serum NULISAseq proteomics, we show that spontaneous menopause is characterized by...

Aging clocks are typically trained on pooled multi-tissue data, implicitly assuming that aging is uniform across organs. Here we challenge this assumption by constructing 49 transcriptomic clocks across 47 tissue types and 2 cell-line categories from GTEx v8 (948 unique donors contributing to the retained clock categories) using donor-grouped cross-validation. Clocks achieved a median Pearson r of 0.543 (best: artery aorta, r = 0.855). We identified 10,253 unique clock genes, of which 69.2%...

While osteoarthritis (OA) has traditionally been viewed as a localized joint disorder, systemic metabolic dysfunction is increasingly recognized as a key contributor to its pathogenesis. Here, we identify a liver-cartilage micronutrient axis in which hepatic dysfunction promotes OA through impaired selenium (Se) metabolism. Nationwide cohorts reveal elevated OA prevalence among individuals with liver disease. In murine models of acute and chronic liver injury and metabolic dysfunction-associated...

Immunosenescence-the age-associated remodeling of the immune system-has emerged as a potential modifier of chronic inflammatory disease. This review examines the evidence that immunosenescence may contribute to the chronicity, refractoriness, and therapeutic heterogeneity of uveitis, and considers the clinical and translational implications of this framework. It first outlines the features of immune aging, including thymic involution, contraction of the naïve T cell pool, accumulation of memory...

CONCLUSION: A significant correlation between fatigue (MF and SPF) and inflammation was found. Among the inflammatory biomarkers investigated, IL-6 showed the most consistent association with both MF and SPF across the included studies.

Intracerebral hemorrhage (ICH), caused by the rupture of blood vessels within the brain parenchyma, represents the most severe form of stroke, characterized by the highest mortality rate and predominantly affecting the elderly population. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as the resident immune cells of the central nervous system and undergo significant metabolic reprogramming following ICH. Microglia exhibit dual roles in post-ICH tissue damage by...

CONCLUSION: Sensory impairment, particularly dual sensory impairment, was most consistently associated with early cognitive deterioration and reduced cognitive recovery. It was not consistently associated with higher dementia progression or mortality transition rates. Death-inclusive multistate modeling may help identify where potentially modifiable sensory impairment is related to cognitive ageing trajectories.

INTRODUCTION: Despite growing interest in age-related cortical mechanisms of postural control, heterogeneity across studies has limited the synthesis of existing evidence. This systematic review aimed to (1) characterize age-related alterations in cortical activity during standing balance tasks with sensory, cognitive, and mechanical challenges; (2) examine the association between cortical activity and postural sway; and (3) characterize the current methodology of assessing cortical activity...

Aging is associated with declining protective immunity and increased autoreactivity, yet the mechanisms linking these processes remain incompletely understood. B lymphocytes are central to this paradox because they integrate antigen recognition, innate signaling, and differentiation under tightly regulated tolerance checkpoints. This review advances the hypothesis that aging appears to drive a progressive, B cell-intrinsic relaxation of central and peripheral tolerance, leading to the...