Aging & Longevity

Partial or transient cellular reprogramming is defined by the limited induction of pluripotency factors without full dedifferentiation of cells to a pluripotent state. Comparing in vitro and in vivo mouse studies, and in vitro studies in humans, supported by visualizations of data interconnections, we show consistent patterns in how such reprogramming modulates key biological processes. Generally, partial reprogramming drives dynamic chromatin remodelling, involving histone modifications that...

Mitochondria, as central regulators of cellular processes such as energy production, apoptosis, and metabolic homeostasis, are essential to cellular function and health. The maintenance of mitochondrial integrity, especially through mitophagy-the selective removal of impaired mitochondria-is crucial for cellular homeostasis. Dysregulation of mitochondrial function, dynamics, and biogenesis is linked to neurodegenerative and metabolic diseases, notably Alzheimer's disease (AD), which is...

As the global human population rapidly ages and diseases of aging become more prevalent, preclinical models of age-related neurodegenerative disorders are increasingly important for identifying early diagnostic biomarkers, monitoring disease progression, and evaluating treatment responsiveness. Rhesus macaques are an ideal species for studies on neurodegeneration due to their phylogenetic relatedness to humans and their complex brain anatomy and physiology. Technological advances in assay...

CONCLUSIONS: These results, highlighting recent increases in female suicides in urban areas and in specific method-specific male suicides both in rural and urban areas, and demonstrating geographical variation across regions, should help guide targeted suicide prevention efforts.

5-hydroxymethylcytosine, also known as the sixth DNA base of the genome, plays an important role in brain aging and neurological disorders such as Alzheimer's disease. However, little is known about its genome-wide distribution and its association with Alzheimer's disease pathology. Here, we report a genome-wide profiling of 5-hydroxymethylcytosine in 1079 autopsied brains (dorsolateral prefrontal cortex) of older individuals and assess its association with multiple measures of Alzheimer's...

Energy management technologies have significant potential to optimize electric vehicle performance and support global energy sustainability. However, despite extensive research, their real-world application remains limited due to reliance on simulations, which often fail to bridge the gap between theory and practice. This study introduces a real-world data-driven energy management framework based on offline reinforcement learning. By leveraging electric vehicle operation data, the proposed...

As China's population continues to age, addressing cognitive decline related to aging has become increasingly important. Simultaneously, rapid economic development has led to rising concerns about lipid metabolism disorders, particularly those involving blood lipids. Identifying modifiable risk factors early is critical to enhancing cognitive function in older adults. Thus, this study focuses on the relationship between triglycerides (TG), high-density lipoprotein (HDL), and cognitive...

Vascular Endothelial Growth Factor (VEGF) is a critical element in vascular dementia (VD) pathogenesis and therapeutic development while remaining strongly influenced by aging processes and cellular aging mechanisms. VEGF's multiple effects comprise neuroprotective functions, its role in vascular development, and its ability to regulate brain blood flow systems, all leading to cognitive preservation. The prefrontal cortex exhibits elevated VEGF gene levels, which directly matches the advancement...

Hematopoietic stem cells (HSCs) ageing is a phenomenon described by reduction in self-renewal capacity, compromised homing, a bias towards myeloid differentiation, and defective reconstitution function. The molecular mechanisms of HSCs ageing have been investigated by several groups. In a broad classification, the underlying causes can be grouped into the intrinsic factors and those related to the microenvironment. Determination of the exact mechanism of HSCs ageing and detailed molecular events...

Meningeal lymphatics serve as an outlet for cerebrospinal fluid, and their dysfunction is associated with various neurodegenerative conditions. Previous studies have demonstrated that dysfunctional meningeal lymphatics evoke behavioral changes, but the neural mechanisms underlying these changes have remained elusive. Here, we show that prolonged impairment of meningeal lymphatics alters the balance of cortical excitatory and inhibitory synaptic inputs, accompanied by deficits in memory tasks....

Chronic stress adversely affects intestinal health, but the specific neural pathways linking the brain to intestinal tissue are not fully understood. Here, we show that chronic stress-induced activation of the central amygdala-dorsal motor nucleus of the vagus (CeA-DMV) pathway accelerates premature aging and impairs the stemness of intestinal stem cells (ISCs). This pathway influences ISC function independently of the microbiota, the hypothalamic-pituitary-adrenal (HPA) axis, the immune...

Thousands of articles were published about the COVID-19 disease and hundreds about the immune response. But still little is known about the features of SARS-CoV-2-specific immunity in elderly. The aim of current research was to evaluate the age-related peculiarities of antibody mediated humoral immune response following SARS-CoV-2 infection. Our study presents an intriguing divergence from the classical concept of immunosenescence, where aging has been assumed to cause poor antibody responses,...

Cellular senescence is a state of permanent loss of proliferative capacity. Therefore, cells that reach a senescent state prevent tumor initiation, acting as an anti-tumor mechanism. However, despite not being proliferative, senescent cells have high secretory activity, constituting the Senescence-Associated Secretory Phenotype (SASP). SASP includes thousands of soluble molecules and extracellular vesicles, through which senescent cells can affect other cells and the extracellular matrix. In...

Following the demographic shift towards an ageing population over the past century, particularly in developed countries, the concept of healthspan has gained increasing acceptance as a key framework for understanding the drivers of healthy ageing. Accordingly, long-lived individuals, such as nonagenarians and centenarians, who remain free from chronic diseases, provide a valuable model to investigate the complex interplay of biological, genetic, and environmental factors that contribute to...

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Previous studies have indicated increased dementia risk associated with fine particulate matter (PM(2.5)) exposure; however, the findings are inconsistent. In this systematic review, we assessed the association between long-term PM(2.5) exposure and dementia outcomes using the Burden of Proof meta-analytic framework, which relaxes log-linear assumptions to better characterize relative risk functions and quantify unexplained between-study heterogeneity (PROSPERO, ID CRD42023421869). Here we...

Prohibitins are a highly conserved family of proteins that have been implicated in a variety of functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation and many others. The human prohibitins prohibitin 1 and prohibitin 2 have been proposed to act as scaffolds within the mitochondrial inner membrane, but their molecular organization has remained elusive. Here we determined the molecular organization of the human prohibitin...

Neutrophils secrete a variety of mediators throughout their lifespan but are mostly associated with pro-inflammatory functions. In this issue of Cell, Hsu et al. describe a new class of extracellular vesicles produced solely by aged neutrophils that elicit anti-inflammatory effects that extend beyond neutrophil lifespan.

The skeleton is one of the most structurally and compositionally diverse organ systems in the human body, depending on unique cellular dynamisms. Here, we integrate prospective isolation of human skeletal stem cells (hSSCs; CD45^(-)CD235a^(-)TIE2^(-)CD31^(-)CD146^(-)PDPN^(+)CD73^(+)CD164^(+)) from ten skeletal sites with functional assays and single-cell RNA sequencing (scRNA-seq) analysis to identify chondrogenic, osteogenic, stromal, and fibrogenic subtypes of hSSCs during development and...

As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study...