Aging & Longevity

No abstract

Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens...

Obstacles to translation elongation stall ribosomes and allow deleterious proteins to accumulate, which threatens cellular health. Cells recognize and clear stalled ribosomes via several interrelated pathways, although the mechanisms by which cells distinguish stalled from normally elongating ribosomes and mount an appropriate response are incompletely understood. While recent work highlights how ribosome collisions help cells to recognize stalled ribosomes, how other factors contribute to...

CONCLUSION: The group-level spatial map showed exploratory correspondence with selected normative functional connectivity (FC)- and structural connectivity (SC)-based candidate profiles. Individualized profiles showed greater cross- sectional correspondence with the selected SC-based profile than with the FC-based profile, providing a network-informed description of diabetic brain alterations.

CONCLUSION: Adult hearing loss is significantly associated with increased risks of cognitive impairment and dementia. These findings highlight the importance of hearing health in cognitive aging and support further prospective and interventional studies.

The core genes of the circadian pathway, such as Timeless(Tim), not only participate in the regulation of biological rhythms, but also play significant roles in DNA damage repair, chronic inflammation, and cellular metabolism. However, it remains unclear whether exercise can delay the age-related phenotypic degeneration by regulating the muscle Tim gene. In here, we first carried out the expression regulation of the muscle Tim gene in the Drosophila by constructing the Mhc-gal4/Tim-UAS system,...

Mutations are fundamental to oncogenesis, yet they cannot fully explain cancer progression, as oncogenic mutations frequently accumulate in healthy tissues without immediate malignancy. In the liver, β-catenin mutations are highly prevalent in hepatocellular carcinoma but are widely considered weak or cooperative drivers, raising the question of how their oncogenic potential is contextually regulated. Aging and chronic injury are major determinants of cancer risk. However, how declining tissue...

Millions of people worldwide suffer from sarcopenia, a clinically recognized syndrome that is defined as the age-related loss of skeletal muscle mass and strength. Sarcopenia reduces mobility, leads to falls and fractures, and increases the risk of death, posing an ever-increasing health-care and economic burden to society. There are currently no approved therapies for the syndrome, partly owing to its multifactorial aetiology, highlighting the need for therapies with pleiotropic beneficial...

Drugs for aging-related diseases may modulate aging itself, but standard clinical trial designs cannot detect such effects. Aging clocks could close this gap, but epigenetic models often yield inconsistent, hard-to-interpret results. In contrast, proteomic clocks, by tracking the immediate effectors of biological change, may excel in providing aging biomarkers or mechanistic insight. Here we compare six proteomic clocks (ProtAge, OrganAge(mortality), OrganAge(chrono), PAC, ipfP3GPT and PAOPAC)...

No abstract

No abstract

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...