Aging & Longevity

The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It...

As the population ages, cognitive decline and neurodegenerative diseases have become major public health concerns. The human gut microbiota plays a major role in regulating neurodevelopment, neuroinflammation, and cognitive decline through the gut-brain axis. Emerging evidence reveals a possible association between alterations in gut microbial diversity and age-related neurological disorders, including Alzheimer's disease and neurodegeneration. Regional and dietary differences shape the gut...

Erzhi Pills (EZP), a traditional Chinese herbal formula, has demonstrated potential aging-modulating properties, while its mechanisms in modulating immunosenescence remain incompletely understood. Two complementary aging murine models were employed to investigate the anti-immunosenescence efficacy of EZP, providing experimental validation for its translational application in delaying age-related immune decline. Morphological and physiological parameters were monitored and thymic/splenic organ...

Cognitive aging reflects underlying biological aging processes and is a key driver of late-life functional outcomes. Emerging evidence indicates that cohabitation with companion animals may influence multiple systemic pathways involved in cognitive aging, yet this potentially modifiable lifestyle factor remains underrecognized. The present narrative review synthesizes current evidence on how companion animals may influence cognitive aging through multilevel pathways, including both direct...

Proteostasis, the maintenance of protein homeostasis, is a critical cellular process for neuronal health that declines with age, contributing to neurodegenerative disease. This review examines the molecular architecture of the proteostasis network, how this is disrupted in ageing neurons, and its impact on neuronal function. We discuss unique challenges posed by the complexity arising from distinct neuronal compartments with distinct functions, as well as neurons' high energy demands, and...

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease that develops in response to chronic epithelial injury. Unlike injury-induced homeostatic lung repair during which fibroblasts undergo apoptosis and clearance, the lungs of IPF patients continue to accumulate apoptosis-resistant, pro-fibrotic, extracellular matrix-producing fibroblasts. Here, we show that prevention of PDGFRα^(+) fibroblast apoptosis by conditional BCL-2 expression leads to the emergence and persistence of...

Intestinal aging characterized by imbalance between cell senescence and mucosal self-renewal, increases susceptibility to the elderly-onset ulcerative colitis (UC), while the underlying mechanisms remain elusive. Here, we identify mRNA N4-acetylcytidine (ac⁴C) modification and its specific writer, N-acetyltransferase 10 (NAT10), as critical regulators of human colonic epithelial cell senescence. Knockdown of NAT10 significantly alleviates human colonic epithelial cell senescence in vitro and...

The rising global burden of pathological aging engenders an urgent need for accessible tools enabling early detection of physical decline, which significantly impacts quality of life and healthcare systems. We hypothesized that speech analysis could capture phenotype-specific signatures of physical deterioration through shared neuromuscular pathways, offering a novel approach to physical assessment. In this study, we employed machine learning to analyze multimodal speech features (acoustic,...

CONCLUSIONS: From 1990 to 2021, there was an overall upward trend in the global burden of ADOD among postmenopausal women. Driven by demographic shifts (population growth and aging) and metabolic risks (particularly high fasting plasma glucose), the burden of postmenopausal women with ADOD is expected to increase substantially. Postmenopausal women in higher SDI countries bore a disproportionately higher ADOD burden, and the SDI-related inequalities among countries widened during the study...

BACKGROUND: Total hip replacement is a successful operation that aims to restore function and quality of life to millions of people globally. Knowing how long a total hip replacement might last is important for patients, surgeons, and health-care institutions for planning and resource allocation. Over the past 20 years, the use of contemporary bearing surfaces for total hip replacement has substantially altered implant wear and, possibly, longevity. To date, there has been no large-scale study...

Age-related macular degeneration (AMD) represents one of the therapeutic challenges of aging eye diseases. Our investigation reveals the stimulator of interferon genes (STING) pathway as an orchestrator of immune-mediated retinal degeneration, exhibiting biphasic, stage-dependent functionality-providing cytoprotection in healthy tissue but driving pathogenic inflammation during early AMD progression. Through immunohistochemical analysis of human eyes, we demonstrate stage-dependent cytoplasmic...

Testosterone production by testicular Leydig cells (LCs) in male mammals is energetically demanding and prone to mitochondrial damage. Despite these challenges, LCs exhibit remarkable longevity and minimal turnover, suggesting the existence of specialized mechanisms that maintain LC mitochondrial homeostasis under such constrains. Here we identify a mitochondrial transfer network between LCs and different testicular macrophage (tMac) subpopulations. Leydig cells release extracellular vesicles...

CONCLUSIONS: Despite gradual increases in the prevalence of impaired physical function during ageing, regular physical activity may help to preserve physical function in older adults.

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Walking is fundamental to human mobility, and slowing gait speed is a widely recognized indicator of aging-related mobility decline. Although mobility decline in older adults has been associated with aging-related neural and morphological changes in muscle, the specific neural and morphological correlates of gait speed remain incompletely characterized. Thus, our primary aim was to quantify how peripheral nerve function, muscle cross-sectional area (MCSA) and intramuscular fat (IMAT) are related...

Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis)...

Resting metabolic rate (RMR) accounts for the majority of the total energy expenditure. While RMR is known to decline with advancing age and is recognized to be lower in females compared to males, the mechanisms underlying these differences remain unclear. Changes in body composition are posited to account for age- and sex-related differences in RMR, but to what extent lacks consensus. We characterized 80 healthy adults aged 23-82 years from the San Diego Nathan Shock Center (SD-NSC) clinical...

Comparative biology plays a crucial role in uncovering fundamental biological mechanisms and providing evolutionary models for their variation. This approach is particularly valuable for studying aging, given the remarkable diversity in aging trajectories across the tree of life. Many evolutionary theories of aging were proposed well before the discovery of the molecular mechanisms involved, and they remain largely theoretical. Moreover, the growing number of model organisms and the expanding...

Across our lifespan, cells divide and differentiate to create the functional units of all organs, yet with age and cancer a small number of cellular families (clones) will rule the fate of the organism. Advances in synthetic and natural barcoding methods now enable cellular ancestries to be reconstructed with unprecedented single-cell resolution. These single-cell lineage-tracing studies are leading to a re-evaluation of long-standing paradigms in development, ageing and cancer biology and are...

Natural killer (NK) cells, a type of potent cytotoxic lymphocyte, are particularly promising for the treatment of cancers that lose or downregulate major histocompatibility complex class I (MHC class I) expression to evade T cell-mediated immunotherapy. However, the hostile and immunosuppressive tumor microenvironment (TME) greatly hinders the function of tumor-infiltrating NK cells, thus limiting the therapeutic efficacy. Here, we show a fusion protein of interleukin 21 (IL-21-Fc) that safely...