Aging & Longevity

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...

No abstract

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...

CONCLUSION: The adoption of mobile health apps must be prioritized to assist individuals with dementia and their caregivers in low income countries. Future apps should focus on improving engagement and involving medical experts in development to increase credibility and utilization across socioeconomic levels and healthcare systems.

Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome...

Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD^(+)) levels are reportedly associated with several aging-related disorders. Thus, supplementation with NAD^(+) precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial effects against these disorders. However, the in vivo metabolic pathways of NMN and NR remain to be elucidated. In this study, we comprehensively analyzed the fate of orally and intravenously administered NMN and NR in...

Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), an alloimmune fibrotic process leading to death or retransplantation after a median of 6 years. Immunosuppression fails to prevent CLAD, suggesting the existence of drug-resistant alloimmune pathways. We used time-of-flight mass cytometry to identify cells enriched in the bronchoalveolar lavage of patients with subsequent acute lung allograft dysfunction (ALAD), a risk factor for CLAD. We show that...