Aging & Longevity

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...

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...

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...

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...

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...

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...

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...

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...

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...

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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...

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...

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...

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...

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.

CONCLUSION: This study highlights the distinct mediating roles of working memory and EEG features in the muscle strength-cognition relationship. Grip strength, as a potential biomarker, may reflect central nervous system integrity and serve as a target for cognitive health interventions in aging populations.

Studies on the human brain have emphasized the loss of gray matter volume and decreased thickness during normal aging, along with variations in the density of small axon fibers across different regions of the corpus callosum (CC). Here, we investigated age-related changes in white matter connectivity in the CC and their association with handedness and cognitive decline in chimpanzees. To this end, microstructural measures of CC morphology were obtained from a sample of 49 chimpanzees. Initial...

The variation of ribosomal (parameter R), satellite III (1q12) (parameter S), and telomere (parameter T) tandem repeats content of the human genome was studied in DNA samples isolated from blood leukocytes of 535 people whose age varied from 5 to 101 years. For analysis we used the method of nonradioactive quantitative hybridization. The group of centenarians (90-101 years old, N = 106) differs from other age groups by a significantly narrower distribution of the ribosomal repeat content in DNA,...

[This retracts the article DOI: 10.1155/2022/7202837.].

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