Aging & Longevity

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,...

CONCLUSION: Higher butyrate intake in individuals aged ≥60 years was linked to better cognitive functioning. This could potentially contribute to maintaining brain function during aging.

Background: One repetition maximum (1RM) testing depends on lifting heavy loads which can put older adults at risk for injury and thus is nonfeasible. Thus, there is a great need for alternative 1RM testing methods, which are safe, patient-friendly, and clinically applicable, in older adults. Notably, aging-induced loss of muscle strength is greater for concentric than eccentric strength. However, there is a lack of information on unique 1RM for concentric and eccentric squat strength. Such...

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young's modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower...

Identifying deficiencies in physical function in older adults is critical to evaluate important health outcomes like sarcopenia, but current protocols are expensive and require complex equipment. This study evaluates the reliability and validity of an inexpensive, simple new Get-Up test in older adults. It involves participants moving quickly from standing upright, to lying flat, then rising to a standing position unassisted. A total of 293 relatively healthy older adults without severe health...

Research on brain aging is crucial for understanding age-related neurodegenerative disorders and developing several therapeutic interventions. Numerous models ranging from two-dimensional (2D) cell-based, invertebrate, vertebrate, and sophisticated three-dimensional (3D) models have been used to understand the process of brain aging. Invertebrate models are ideal for researching conserved aging processes because of their simplicity, short lifespans, and genetic tractability. Moreover, vertebrate...

With rapid advancements in single-cell RNA sequencing (scRNA-seq) technologies, exploration of the systemic coordination of critical physiological processes has entered a new era. Here, we generated a comprehensive Arabidopsis single-nucleus transcriptomic atlas using over 1 million nuclei from 20 tissues encompassing multiple developmental stages. Our analyses identified cell types that have not been characterized in previous single-protoplast studies and revealed cell-type conservation and...

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Elevated heme levels, a consequence of hemolysis, are strongly associated with increased susceptibility to bacterial infections and adverse sepsis outcomes, particularly in older populations. However, the underlying mechanisms remain poorly understood. Using a cecal ligation and puncture (CLP) model of sepsis, we demonstrate that elevated heme levels correlate with Kupffer cell loss, increased bacterial burden, and heightened mortality. Mechanistically, we identify mitochondrial damage as a key...

CONCLUSIONS: The results of this study showed that sustained long-term trajectories of adequate levels of PA and SB are associated with lower rates of SO. The findings of this study support the evidence that regular PA can help reduce the likelihood of developing SO.

This study investigates the relationship between physical activity (PA) levels and DNA methylation (DNAm)-predicted epigenetic clocks in a U.S. population sample (n = 948, mean age 62, 49% female). Eight epigenetic clocks were analyzed, revealing that higher PA levels were significantly associated with younger biological ages across all indicators, with the strongest effects observed for SkinBloodAge and LinAge. Multivariable linear regression models, adjusted for sociodemographic and lifestyle...

Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by the early hallmark, hippocampal synaptic loss. However, the impact and mechanistic role of gut microbiota in hippocampal synapse loss during aging remains unclear. Here, we observed that the fecal microbiota of naturally aged mice successfully transferred cognitive impairment and hippocampal synapse loss to young recipients. Multi-omics analysis revealed...

Telomeres are the nucleoprotein structures at chromosome ends. Telomeres are particularly sensitive to oxidative stress, which can induce telomere damage, shortening, and premature cellular senescence. How oxidative damage influences telomere structure has not been defined. Here, we induce oxidative damage at telomeres using menadione, which damages mitochondria mimicking intrinsic oxidative stress. We find that oxidative stress induces at telomeres single-stranded DNA breaks, internal DNA loop...