Aging & Longevity

The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a^(R878H/+)), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-related changes in the bone marrow microenvironment. Mutant...

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Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion...

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Environmental enrichment (EE) represents a robust experimental framework exploring the intricate interplay between genes and the environment in shaping brain development and function. EE is recognized as a non-invasive intervention, easily translatable to elderly human cohorts, and extrapolated from research on animal aging models. Age is the most important risk factor for ischemic stroke. Research indicates that EE, characterized by increased sensory, cognitive, and social stimulation, leads to...

H3 K27-altered spinal cord diffuse midline glioma (H3-SCDMG) poses therapeutic challenges. Analysis of 73 clinical samples revealed heightened proliferation in H3-SCDMG versus wild-type tumors, suggesting therapeutic vulnerabilities. Drug screening identified cytarabine (Ara-C) as highly effective in inhibiting proliferation in H3 K27M cell models, recently established patient-derived cells, and patient-derived xenograft models. Mechanistically, Ara-C can suppress tumor growth through DNA...

Aging is associated with dysregulated methionine metabolism and increased levels of enzymes in the tyrosine degradation pathway (TDP). To investigate the efficacy of targeting either methionine metabolism or the TDP for healthspan improvement in advanced age, we initiated dietary MetR or TDP inhibition in 18-month-old C57BL/6J mice. MetR significantly improved neuromuscular function, metabolic health, lung function, and frailty. In addition, we confirmed improved neuromuscular function from...

BackgroundAccurate classification of cognitive impairment in population studies is challenging.ObjectiveTo compare the performance of a diagnostic algorithm with a clinical consensus panel.SampleIn 2016, the Health and Retirement Study (HRS) implemented the Harmonized Cognitive Assessment Protocol Project (HRS-HCAP) to streamline cognitive assessments for select HRS participants.MethodsThe Manly-Jones HCAP diagnostic classification was used to classify cognitive status as normal, mild cognitive...

ObjectivesFew studies have investigated health outcomes associated with arthritis in low-middle-income countries. Our objective was to examine the association between arthritis and all-cause hospitalization and mortality among middle-aged and older adults in Mexico.MethodsOur sample included 12,106 participants aged >50 years from the 2012, 2015, and 2018 waves of the Mexican Health and Aging Study. Logistic regression was used for the associations between arthritis and hospitalization....

Older women may experience elevated depression symptoms, which have been associated with morbidity and mortality. Yet, few studies have examined associations of depression symptoms with longevity. We examined associations among older women of depression symptoms with survival to ages 90, 95, and 100, and survival to age 90 with intact mobility and cognitive functioning. Participants were 70,560 women enrolled in the Women's Health Initiative with potential, due to birth year, to reach age ≥ 90...

Efficient upcycling of uranyl from uranyl-containing radioactive organic wastewater is of utmost importance for the sustainable development of nuclear energy. In this work, an indirect electrochemical method to upcycle uranyl from radioactive organic wastewater is proposed. A cost-efficient self-standing polyarylether-based covalent organic framework electrode (PAE-COF-AO@CC) not only acts as an oxygen reduction reaction (ORR) catalyst for hydrogen peroxide (H(2)O(2)) production, but also...

The regeneration of myelin in the central nervous system (CNS) reinstates nerve health and function, yet its decreased efficiency with aging and progression of neurodegenerative disease contributes to axonal loss and/or degeneration. Although CNS myeloid cells have been implicated in regulating the efficiency of remyelination, the distinct contribution of blood monocytes versus that of resident microglia is unclear. Here, we reveal that monocytes have non-redundant functions compared to...

Organismal aging has been associated with diverse metabolic and functional changes across tissues. Within the immune system, key features of physiological hematopoietic cell aging include increased fat deposition in the bone marrow, impaired hematopoietic stem and progenitor cell (HSPC) function, and a propensity towards myeloid differentiation. This shift in lineage bias can lead to pre-malignant bone marrow conditions such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal...

In this study, we investigated the contribution of rare coding variants to human longevity by analyzing whole exome sequencing data from 1245 German long-lived individuals (LLI) and 4105 geographically matched younger controls. We identified novel exome-wide significant associations at both the single-variant and gene level, with a significant over-representation of genes involved in mechanistic target of rapamycin (mTOR) signaling. As such, three rare single variants in the mTOR-pathway genes...

INTRODUCTION: Allostatic load (AL) is a composite score of progressive physiological dysregulations in response to long-term exposure to everyday stress. Despite growing interest, limited research has focused on links with cerebral and cognitive aspects of aging and with markers sensitive to Alzheimer's disease (AD) in a healthy elderly population and with a multimodal approach.

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Animals select food based on hungers that reflect dynamic macronutrient needs, but the hormonal mechanisms underlying nutrient-specific appetite regulation remain poorly defined. Here, we identify tachykinin (Tk) as a protein-responsive gut hormone in Drosophila and female mice, regulated by conserved environmental and nutrient-sensing mechanisms. Protein intake activates Tk-expressing enteroendocrine cells (EECs), driving the release of gut Tk through mechanisms involving target of rapamycin...

CONCLUSION: This study identifies key risk factors associated with cognitive impairment in older Kuwaiti adults. These findings underscore the need for targeted interventions to mitigate cognitive decline in aging populations and provide context-specific data to support policy decisions.

CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptides have emerged as key regulators of plant-microbe interactions, including arbuscular mycorrhizal (AM) symbiosis. Here, we identify Medicago truncatula CLE16 as a positive regulator of AM symbiosis. MtCLE16 is expressed in root cells colonized by AM fungi (AMF) and its overexpression within colonized tissues increases arbuscule abundance by finetuning their growth and lifespan. Functional and transcriptomic analyses reveal that MtCLE16 acts...

Humans often live in neighborhoods, nested socio-spatial clusters within settlements of varying size and population density. In today's cities, neighborhoods are often characterized as relatively homogenous and may exhibit segregation along various socioeconomic dimensions. However, even within neighborhoods of similar social or economic status, there is often residential disparity, which in turn impacts perceived inequality. Drawing on the Global Dynamics of Inequality (GINI) project database,...