Aging & Longevity

There is increasing recognition that a broader array of biological changes may contribute to the clinical expression of cognitive decline. As such, an emerging and often overlooked consideration in dementia is apathy, gait dysfunction, motoric-cognitive risk syndrome, and their interplay. Broadly, apathy, gait dysfunction, and motoric-cognitive risk may reflect changes across multiple physiological and neural systems acting as clinical markers bridging normal aging and overt dementia, thereby...

Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to...

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, and its pathogenesis and treatment strategies remain major challenges. Recent advances in single-cell RNA sequencing and lineage tracing have revealed that vascular smooth muscle cells (VSMCs) are not merely passive structural components of atherosclerotic plaques, but highly plastic participants that undergo clonal expansion, phenotypic modulation, and transdifferentiation into functionally diverse cell states....

Recent advances in biomarker profiling, wearable sensing, and high-density longitudinal self-monitoring have generated detailed individual-level datasets demonstrating that many ageing-associated measures, including cardiometabolic markers, inflammatory signals, functional performance metrics, and epigenetic age estimates remain highly modifiable in adulthood. However, these data also reveal substantial heterogeneity in response timescales and durability, with rapid reversibility of many...

CONCLUSIONS: Stomach cancer mortality rates declined substantially among adults aged 65 years or older, but absolute deaths declined less because demographic growth and ageing offset epidemiological gains, with burden increasingly concentrated at the oldest ages. Progress should therefore be assessed using both age-standardised rates and absolute burden.

Vascular endothelial senescence is a pivotal driver of age-related pathologies. Metabolism plays a critical regulatory role in endothelial cell senescence. Our previous studies have shown that deficiency of DHCR24, a gene involved in lipid metabolism, promotes endothelial cell senescence. However, how DHCR24 participates in endothelial cell senescence through lipid metabolism remains unclear. Using endothelial-specific DHCR24 knockout mice and replicative senescent human umbilical vein...

Aging is frequently perceived negatively due to its association with declines in brain and motor function yet not all aspects of brain function are equally affected. The cerebellum, a brain region closely linked to motor control, undergoes clear structural changes with age, but the impact of this degeneration on cerebellar function remains debated. The present study thoroughly investigates the impact of age on cerebellar function by measuring cerebellar motor and cognitive performance across the...

Early-life nutrition may influence lifelong ageing, yet human evidence is scarce. Using Britain's postwar sugar rationing as a natural experiment, we examine its long-term effects in 64,809 United Kingdom Biobank participants. Exposure to sugar rationing during the first 1,000 days of life is associated with a 9% lower incidence of hallmark-related disease, with a hazard ratio of 0.91 and a 95% confidence interval of 0.88-0.94, and a 19% lower risk of all-cause mortality, with a hazard ratio of...

Chronic kidney disease (CKD) is increasingly recognized as a model of accelerated biological aging, characterized by premature cardiovascular disease and frailty. Although frailty has become a cornerstone of gero-nephrology, current frailty models primarily emphasize physical performance and functional decline, providing limited insight into the vascular mechanisms underlying biological vulnerability. Conversely, vascular aging is traditionally framed within cardiovascular medicine, with little...

Brain regions are organized into large-scale networks through dynamic functional connections that support sensorimotor and cognitive processes across the lifespan. Age-related disruptions of these functional systems are associated with cognitive and motor decline and increased risk of neurocognitive disorders. A growing body of evidence suggests that structured physical training can modulate resting-state functional connectivity within these networks, offering a potential neuroprotective...

Interventions that disrupt growth hormone (GH) action are recognized as some of the most potent methods for extending lifespan. Accordingly, GH receptor antagonists (GHA) represent potential therapeutics to improve healthspan. Somavert (Pegvisomant for injection), used for treating patients with acromegaly, is currently the only FDA approved GHA. This drug was based on our laboratory's early 1990s discovery that mutating a codon for a conserved glycine-at position 119 in bovine GH or 120 in...

Infections remain a major cause of mortality and may threaten healthy aging. Previous studies have focused on isolated severe infections rather than longitudinal infection burden. We aimed to examine associations of infection trajectories with biological age acceleration (BAA) and assessed infection severity and genetic susceptibility. We included adults aged 20-74 years from the Shanghai Suburban Adult Cohort and Biobank, China, enrolled between 2016 and 2019 with valid biological age (BA)...

CONCLUSION: Translational development faces several barriers, including poor blood-brain barrier (BBB) penetration, off-target neurotoxicity, uncharacterised long-term safety and limited generalisability from APP/PS1 models lacking tauopathy. All MERCS-targeted and senolytic combinatorial strategies discussed herein represent prospective pre-clinical research directions rather than mature clinical therapeutic approaches. We propose an experimental roadmap based on conditional knockouts,...

With accelerating population aging, age-related bone loss, osteoporosis, and delayed bone defect repair have become major challenges in regenerative medicine. Bone aging is not caused by the decline of a single cell type, but is a multilevel pathological process driven by the continuous coupling and mutual reinforcement of intracellular damage accumulation, senescence signal propagation, and microenvironmental deterioration. Based on established aging theories, this review integrates...

Working memory is one of the core cognitive functions that declines in older adulthood. Brain reserve (BR) refers to neurobiological status of the brain that supports cognition, offering a valuable neurostructural framework for understanding working memory decline among older adults. However, most existing studies rely on gross, whole-brain measures of BR which may lack sensitivity to specific cognitive functions, and few studies have examined their sex differences. Based on 131 healthy older...

Cardiovascular ageing is accompanied by progressive impairment of redox buffering, mitochondrial quality control, proteostasis and metal homeostasis. Iron and copper homeostasis, together with cystine-glutathione and thiol/disulfide redox metabolism, are increasingly recognized as interconnected determinants of metabolic vulnerability and regulated cell death (RCD) in age-related cardiovascular diseases. Ferroptosis, defined by iron-dependent lipid peroxidation and impaired anti-peroxidative...

Neuromodulation aims to improve brain function by altering neural activity. While many rehabilitation strategies seek to restore normal, healthy-like dynamics, some adopt a complementary strategy, using neuromodulation to strengthen repurposed processes that support function. Here we formalize these approaches as 'restorative normalization' (RN) and 'compensatory amplification' (CA), respectively. Drawing on cognitive neurophysiology, we evaluate the following four factors that enable CA to be...

Androgenetic alopecia (AGA) is the most common form of non-scarring hair loss, driven by genetic factors and increased sensitivity of scalp hair follicles to dihydrotestosterone (DHT), which causes progressive miniaturization of dermal papilla cells and shortens the hair growth phase. The precise molecular pathogenesis of AGA remains incompletely understood. The study aimed to elucidate the regulatory mechanism between secreted frizzled-related protein 2 (SFRP2) and follistatin-like 1 (FSTL1),...

Suppression of growth hormone (GH) signaling is known to be effective to extend lifespan in mammals, yet most models rely on congenital disruption of the GH/insulin-like growth factor-1 (IGF-1) axis. Whether modulation of this pathway later in life can still influence aging and the underlying cellular mechanisms remains incompletely understood. To address this, we ablated the growth hormone receptor (Ghr) at 12-months of age in mice (12mGHRKO), using a tamoxifen-inducible model. Midlife Ghr...

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