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Circadian rhythm disruption is recognized as a feature of aging and neurodegenerative disease, yet whether intrinsic cellular circadian properties relate to underlying processes in humans remains unknown. We measured intrinsic circadian period and its deviation from 24 h (Δ-period) using ex vivo bioluminescence in dermal fibroblasts from 135 older adults with cognitive complaints. Associations with plasma biomarkers (pTau-217, neurofilament light chain [NfL], and glial fibrillary acidic protein...

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...

The warning signs included a web search, a mother’s doubts, and inklings of a “sexist attitude”

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...

N-bridged [3.2.1]octanes (tropanes) and their related bridged bicyclic systems constitute highly sought-after scaffolds in drug discovery and development. Notably, the enantioselective synthesis of chiral 3-aryltropanes which are compounds widely distributed across bioactive pharmaceutical agents remains underdeveloped. Tropinone is a readily available and cost-effective starting material. By initiating the synthesis from tropinone, it is possible to substantially lower the synthesis costs. Here...

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...