Aging & Longevity
Glucagon receptor signaling is indispensable for the healthspan effects of caloric restriction in aging male mice
Obesity and type 2 diabetes mellitus accelerate aging, shortening the duration of healthspan. Conversely, chronic calorie restriction (CR) extends healthspan. Research aimed at understanding the mechanism by which CR slows aging has focused heavily on insulin and downstream signaling cascades. Glucagon, a hormone that counter-regulates insulin, is commonly affected by these same interventions. To investigate the role of glucagon in aging, we used dietary manipulation, global and liver-specific...
Network analysis of sleep disorders, depression and anxiety symptoms among community older adults
CONCLUSIONS: The central symptoms and their intricate connections in the network play an importance role in gaining the underlying pathological mechanisms, as well as potential interventions for comorbidity in community older adults.
Association between preoperative frailty to adverse postoperative outcomes in older people undergoing elective spinal surgery: a prospective cohort study
CONCLUSIONS: In geriatric elective spine surgery, preoperative assessment using the Frailty Screening Scale can help identify patients at potentially higher risk for postoperative adverse events. However, further high-quality studies are warranted to investigate the reliability of brief frailty assessments in predicting postoperative outcomes.
Association between simplified anthropometric age and functional performance metrics in older Chinese adults: A study on muscle strength, sit-to-stand ability, and gait speed
CONCLUSION: S-AnthropoAge shows modest advantages over CA in correlating with key physical function measures (HGS, FTSST) and may complement CA in assessing functional aging.
Population-based estimates of healthy working life expectancy in China
CONCLUSION: The healthy working life expectancy at 60 years old in China exceeds the targeted retirement age of 65. Salient socioeconomic and geographic variations of healthy working life expectancy exist in China.
CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma
Cholangiocarcinoma (CCA) remains a lethal malignancy with limited therapeutic options. Through genome-wide CRISPR-Cas9 screening, we identified the adenosine triphosphatase (ATPase) valosin-containing protein (VCP) as a critical dependency in CCA. Compound screens revealed that the VCP inhibitor CB-5339 potently suppresses CCA proliferation in a panel of patient-derived organoids by inducing cellular senescence. It is known that senescent cells persist, and this can contribute to therapy...
Impaired macroautophagy in oligodendrocyte precursor cells suppresses neuronal plasticity via a senescence-associated signaling
Aging drives cognitive decline in the adult brain with unclear mechanisms. Previously, oligodendrocyte precursor cells (OPCs), the source cells of myelin-forming cells in the central nervous system, have been linked to brain aging by their compromised differentiation and regeneration capability. Whether a myelination-independent function of OPCs is involved in brain aging remains unknown. In this study, we herein report a myelination-independent role of OPCs in exaggerating cognitive decline in...
Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice
The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), primarily localized in cell membranes, where they govern membrane biophysical properties. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, which is associated with normal age-related reductions in contrast sensitivity, diminished photoreceptor function and delayed rod-mediated dark adaptation recovery, and pathological age-related macular degeneration...
Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during replicative aging
Clathrin-mediated endocytosis (CME) is a critical cellular process that regulates nutrient uptake, membrane composition, and signaling. Although replicative aging affects many cellular functions, its impact on CME remains largely unknown. We show that in budding yeast, older cells have slower assembly of early and coat CME modules, resulting in longer endocytic turnover and reduced Mup1 internalization. This change in CME dynamics is mother cell-specific, and not observed in daughters. Our data...
Air pollution and impulsive choice in aging: evidence from delay discounting
Heightened air pollution exposure is associated with an increased risk for developing neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, yet it is unclear how pollution impacts the aging brain more broadly. Rodent research has shown that higher air pollution exposure is associated with increased impulsive behavior, operationalized as a preference for immediate reward in delay discounting tasks. We examined this relationship in middle-aged and older humans by...
Frontoparietal functional dedifferentiation during naturalistic movie watching among older adults at risk of emotional vulnerability
Functional dedifferentiation, a hallmark of brain aging particularly evident within the frontoparietal network (FPN), has been extensively investigated in the context of cognitive decline, yet its implications for late-life mental health remain poorly understood. Leveraging naturalistic paradigm combined with gradient mapping techniques, the present study investigated FPN functional dedifferentiation-quantified by functional dispersion of FPN in the multidimensional gradient space-during...
The relationship between category-level neural differentiation and exploratory eye movements in healthy young and older adults
Age-related neural dedifferentiation, characterized by lower selectivity of neural responses in high-level sensory cortex, is thought to be a major contributor to age-related cognitive decline. However, the mechanisms that underlie dedifferentiation are poorly understood. Building on prior evidence that exploratory eye movements differ with age, we investigated the role that eye movement might play in age-related declines in neural selectivity. Healthy young and older adults underwent fMRI with...
A Rare Hematopoietic Stem Cell-Derived Megakaryocyte Progenitor Accumulates via Enhanced Survival and Contributes to Exacerbated Thrombopoiesis Upon Aging
Distinct routes of cellular production from hematopoietic stem cells (HSCs) have defined our current view of hematopoiesis. Recently, we and others have challenged classical views of platelet generation, demonstrating that megakaryocyte progenitors (MkPs) and ultimately platelets can be specified via an alternate and additive route of HSC-direct specification specifically during aging. This "shortcut" pathway generates hyperactive platelets likely to contribute to age-related platelet-mediated...
Mitochondrial respiratory chain deficiency is associated with an impaired skeletal muscle regenerative response and fibrosis in older men with HIV
Despite suppressive anti-retroviral therapy (ART), some older people with HIV show adverse ageing phenotypes, and the underlying mechanisms remain incompletely understood. We recruited 30 men with HIV aged ≥ 50 years and 15 well-matched men without HIV and performed histological analyses on skeletal muscle biopsies and plasma biomarker measurement, in combination with clinical and functional assessments. Men with HIV showed higher frequencies of frailty, pre-frailty, sarcopenia, and...
Publisher Correction: Rejuvenation of aged oocyte through exposure to young follicular microenvironment
No abstract
Impaired early type I interferon responses to influenza virus infection in aged mice are associated with subsequent increased pulmonary inflammation
Seasonal influenza is responsible for significant mortality and morbidity worldwide. Seventy to ninety percent of these deaths occur in those aged 65 or older. To determine the innate immune responses to influenza A virus (IAV) infection, young (12-week) and old (70-week) C57BL/6 J mice were infected intranasally (i.n.) with IAV PR8. Immune responses were determined by qRT-PCR and single-cell RNA sequencing (scRNA-seq). Old mice, as compared to young mice, had significantly higher viral loads...
Aging Reduces Intestinal Stem Cell Activity in Killifish and Intermittent Fasting Reverses Intestinal Gene Expression Patterns
The process of aging is associated with a decline in cell, tissue, and organ function, leading to a range of health problems. Increasing evidence indicates that dietary restriction can counteract age-dependent effects and improve health and longevity in whole organisms, but less is known about the influence of aging and the impact of nutrition on individual organs of an organism. In this study, we examined the intestine of the very short-lived aging model system, the African turquoise killifish...
Regional modulation of neurodegeneration and microglial activation by intravenous Wharton's jelly mesenchymal stromal cell therapy in a mouse model of amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition characterized by rapid degeneration of motoneurons (MNs), leading to progressive muscle atrophy and, ultimately, mortality within a few years of diagnosis. Although the precise mechanisms initiating MN degeneration are not fully understood, the involvement of non-neuronal cells, including microglia, in ALS pathophysiology is increasingly recognized. Mesenchymal stromal cell (MSC)-based therapies have emerged as a...
Impact of adult son migration on the health wellbeing of older parents and shifts in caregiving patterns: a study in India
CONCLUSION: Parents of migrants often experience poorer health, chronic morbidity, psychological distress, and loneliness compared to parents of non-migrants. Despite family members being primary caregivers, parents of migrants were more likely to rely on non-family caregivers and take on financial responsibility for their care. The study highlights the need for eldercare strategies to address the caregiving gaps in areas with high adult out-migration, particularly considering generational and...
Explainable machine learning for early detection of Parkinson's disease in aging populations using vocal biomarkers
INTRODUCTION: Parkinson's Disease (PD) is a progressive neurodegenerative disorder that significantly affects the aging population, creating a growing burden on global health systems. Early detection of PD is clinically challenging due to the gradual and ambiguous onset of symptoms.
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