Aging & Longevity

TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations....

Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels,...

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CONCLUSION: Our findings indicate that a substantial proportion of older adults experience digital exclusion, particularly in China. Digital exclusion demonstrates a positive association with loneliness, suggesting that enhancing digital inclusion may serve as a critical strategy for alleviating loneliness and mitigating psychological distress in ageing populations.

Current obesity classifications may not adequately reflect age- and gender-specific risks in diverse populations. In a prospective cohort study of 166,285 Chinese adults aged ≥40 years without prior cardiovascular disease (CVD) or cancer, we evaluate optimal thresholds of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting incident CVD and all-cause mortality. We observe monotonically increasing dose-response associations of BMI, WC, and WHR with CVD risk...

Reactive oxygen species (ROS) influence cell proliferation and fate decisions by oxidizing cysteine residues (S-sulfenylation) of proteins, but specific targets and underlying regulatory mechanisms remain poorly defined. Here, we employ redox proteomics to identify cell-cycle-coordinated S-sulfenylation events and investigate their functional role in proliferation control. Although ROS levels rise during cell cycle progression, the overall oxidation of the proteome remains constant, with dynamic...

CONCLUSIONS: Aerobic exercise mitigates AGEs-induced muscle deterioration through molecular and structural improvements. SAF and CML may serve as noninvasive biomarkers of functional decline in older adults. These findings highlight the potential of exercise to counteract sarcopenia associated with AGEs accumulation.

Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the "hygiene hypothesis." This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission's deworming...

How societies remember the dead can reveal what people value in life. We analyzed 38 million obituaries from the United States to examine how personal values are encoded in individual and collective legacies. Using Schwartz's theory of basic human values, we found that tradition and benevolence dominated legacy reflections, while values like power and stimulation appeared less frequently. Major cultural events-the terrorist attacks of September 11th, the 2008 financial crisis, and the COVID-19...

Ageing of the haematopoietic system is characterized by phenotypic and functional impairments that are driven by alterations of haematopoietic stem cells and of the bone marrow niche. Haematopoietic stem cells are responsible for the production of all the different cell types that constitute the blood, and their maintenance and differentiation must be tightly regulated during the whole life of an organism. Exciting new data emphasize that central aspects of blood ageing, ranging from...

Cognitive Frailty (CF) is a clinical syndrome characterized by the co-occurrence of physical frailty and cognitive impairment in the absence of dementia. This geriatric condition has emerged as a significant contributor to compromised health status and diminished quality of life among aging populations, yet its underlying pathological mechanisms remain incompletely elucidated. Chronic low-grade inflammation, recognized as a hallmark of biological aging, has been implicated in the pathogenesis of...

CONCLUSIONS AND IMPLICATIONS: This study revealed the beneficial effects of music imaging on cognitive function, neuropsychiatric symptoms, sleep quality, and quality of life among older adults with MCI. These findings support the application of music imaging among older adults with MCI with the aim of slowing cognitive decline, improving symptoms, and promoting healthy aging. [The study was registered with the China Clinical Trial Registry (ChiCTR2400081469) and approved by the Ethics Committee...

CONCLUSION AND IMPLICATIONS: An NLP-based model using EMS text data could improve the identification of frequent users. Integration of such tools into prehospital care systems may support earlier identification and tailored intervention strategies for older people frequent in use of acute care.

Neuroblastomas encompass malignant cells with varying degrees of differentiation, ranging from adrenergic (adr) cells resembling the sympathoadrenal lineage to undifferentiated, stem-cell-like mesenchymal (mes) cancer cells. Relapsed neuroblastomas, which often have mesenchymal features, have a poor prognosis and respond less to anticancer therapies, necessitating the development of novel treatment strategies. To identify novel treatment options, we analyzed the sensitivity of 91 pediatric cell...

Mitochondrial dynamics enable cellular adaptation to fluctuations in energy demand, such as those imposed on skeletal muscle by exercise, metabolic disorders, or aging. Here, we report a novel pathway that modulates mitochondria dynamics in skeletal muscle involving the scaffolding protein ankyrin-B. Rare variants in ankyrin-B, encoded by ANK2, increase risk for cardio-metabolic syndrome in humans and mice. We show that mice selectively lacking skeletal muscle ankyrin-B have reduced endurance...

The increasing global prevalence of diabetic nephropathy poses substantial health and economic burdens. Currently, effective anti-fibrotic therapies for managing kidney fibrosis associated with chronic kidney disease are lacking. This study reveals corisin, a microbiota-derived peptide, as a central driver in the progression of diabetic kidney fibrosis. Corisin levels were found to be markedly elevated in the serum of diabetic chronic kidney disease patients relative to healthy controls, with...

Recent advancements in cancer immunotherapy have improved patient outcomes, yet responses to immunotherapy remain moderate. Immunosenescence has been shown to contribute to the development and progression of various diseases; however, its specific role in solid tumors has not been fully delineated. Here we conducted a phase 2 clinical trial involving 51 patients with cancer undergoing neoadjuvant chemoimmunotherapy and applied single-cell RNA as well as TCR and BCR sequencing on tumor and blood...

BACKGROUND: Chronic pain (CP) and psychiatric disorders (PD) are common in older adults, and they both may significantly impact patients' functioning and quality of life. However, research on the prevalence and impact of CP in people with PD remains limited- especially in older adults- and psychiatric care often neglects somatic comorbidities.

Each year, billions of animals migrate across the globe on diverse spatial and temporal scales. Migration behavior thus plays a fundamental role in the life cycle and Darwinian fitness of many organisms. While the influence of migration on early-life survival and reproduction is well documented, its effects on senescence (aging) in advanced age remain largely unexplored. Using a unique 44-y ring-resighting dataset from a long-lived, partially migratory bird species, the Greater Flamingo...

The fast-paced improvements in mortality in high-income countries since the early 1900s have led to a sustained increase in life expectancy. However, whether this linear trend will continue or life expectancy gains will decelerate in the near future remains unclear. To answer this question, we apply multiple established and recently developed mortality forecasting methods to estimate cohort life expectancy for individuals born between 1939 and 2000 in 23 high-income countries. Across all...