Aging & Longevity
A receptor for glycation end products (RAGE) is a key transmitter between garb-aging and inflammaging
A receptor for glycation end products (RAGE) plays a key role in the pathogenesis of many chronic diseases associated with aging. Acting as a multi-ligand sensor, RAGE is able to bind a wide range of stimuli, which fuels inflammation. This makes it a key link between garb-aging and inflammaging. We propose that RAGE functions as the missing molecular link between garb-aging, the progressive buildup of biological waste, and inflammaging, the chronic inflammatory state that drives degenerative...
Increased nucleotide metabolism alleviates Alzheimer's disease pathology
Genetic information in cells flows from DNA to RNA to proteins, which form molecular machines. During normal ageing, cell intrinsic and environmental factors alter this flow of information by damaging DNA in cells, including postmitotic neurons. Damage to DNA is associated with age-related neurodegenerative diseases such as Alzheimer's disease (AD). We previously reported an increase in DNA repair mechanisms in a fly model of AD. However, the causal mechanisms underlying somatic mutations in AD...
Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel
Sortilin (SORT1) is a lipoprotein receptor that shows genome-wide association with hypercholesterolaemia, explained by its ability to control hepatic output of lipoproteins. Although SORT1 also shows genome-wide association with Alzheimer disease and frontotemporal lobe dementia, the most prevalent forms of age-related dementias, sortilin's contribution to human brain lipid metabolism and health remains unclear. Here we show that sortilin mediates neuronal uptake of polyunsaturated fatty acids...
The ganglioside GD3 and its synthase (ST8SIA1) as novel senescence markers associated with osteoarthritis
Osteoarthritis (OA) is the most common age-induced degenerative joint disease associated with synovial inflammation, subchondral bone remodeling, and cartilage degradation. One of the significant emerging causes of OA progression is senescent cell accumulation within the joint compartment during lifespan. Currently, there are no therapeutic approaches nor stratification tools that rely on the senescence burden in OA. In this study, we identified the b-series ganglioside 3 (GD3) as new senescent...
Sex specific gut bacterial community structure: implications for frailty risk in people with HIV
Frailty is a major health concern associated with aging and has been linked to gut microbiome composition, especially in elderly individuals needing care. People with HIV (PWH) present high risk of early-onset frailty. This study examines the relationship between frailty and the gut microbiome, with an emphasis on sex-based differences in PWH. Data were drawn from 268 participants in the New Orleans Alcohol Use in HIV (NOAH) Study, including 16S microbiome sequencing from stool samples, cytokine...
MRI-based multi-organ clocks for healthy aging and disease assessment
Biological aging clocks across organ systems and tissues have advanced understanding of human aging and disease. In this study, we expand this framework to develop seven magnetic resonance imaging-based multi-organ biological age gaps (MRIBAGs), including the brain, heart, liver, adipose tissue, spleen, kidney and pancreas. Using data from 313,645 individuals curated by the MULTI Consortium, we link the seven MRIBAGs to 2,923 plasma proteins, 327 metabolites and 6,477,810 common genetic...
Vitamin C conveys geroprotection on primate ovaries
Ovarian aging plays a pivotal role in female reproductive health, with implications for treatment strategies and quality of life. However, the potential of a single pharmaceutical agent to mitigate primate ovarian aging remains largely unexplored. Our 3.3-year study in monkeys demonstrates that oral vitamin C has geroprotective effects against ovarian aging. Vitamin C diminishes key aging biomarkers, including oxidative stress and follicular depletion. Using a single-cell transcriptomic clock,...
Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study…
BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and...
Global age-sex-specific all-cause mortality and life expectancy estimates for 204 countries and territories and 660 subnational locations, 1950-2023: a demographic analysis for the Global Burden of Disease Study 2023
BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with...
Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023
BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of...
Solution-processable and photo-curable system for low-cost and scalable transient electronics
The discovery of non-toxic, bioresorbable silicon electronics is a major breakthrough in the fields of transient, dissolvable biomedical implants and environmental monitors, as it opens up the possibility of producing versatile components based on established semiconductor processes. However, given the limited lifespan of such electronics, it is essential to consider economical manufacturing and production strategies that reduce the unit price for commercialization. Here, we introduce a...
The geroprotective potential of chalcones
Aging is the most important risk factor for multiple pathologies including cardiovascular, neoplastic, metabolic and neurodegenerative diseases. Potential geroprotective strategies involve lifestyle-related, nutritional and pharmacological interventions. Recently, chalcones, a subgroup of secondary plant metabolites, have gained attention. 4,4'-dimethoxychalcone was the first chalcone to be shown to mediate geroprotection and lifespan extension across different species. Several other chalcones...
Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance
The insulin receptor entrains tissue growth and metabolism to nutritional conditions. Complete loss of function in humans leads to extreme insulin resistance and infantile mortality, while loss of 80-90% function permits longevity of decades. Even low-level activation of severely compromised receptors, for example by anti-receptor monoclonal antibodies, thus offers the potential for decisive clinical benefit. A barrier to genetic diagnosis and translational research is the increasing...
Niche-specific dermal macrophage loss promotes skin capillary ageing
All mammalian organs depend on resident macrophage populations to coordinate repair and facilitate tissue-specific functions^(1-3). Functionally distinct macrophage populations reside in discrete tissue niches and are replenished through a combination of local proliferation and monocyte recruitment^(4,5). Declines in macrophage abundance and function have been linked to age-associated pathologies, including atherosclerosis, cancer and neurodegeneration^(6-8). However, the mechanisms that...
Age, glucose tolerance, and cognitive performance in female vervet monkeys
This study assessed relationships between age, glucose and insulin metabolism, and cognitive performance in vervet monkeys (Chlorocebus aethiops sabaeus) a valuable model for aging research. Executive function, working memory, body mass index (BMI), and glucose and insulin responses during intravenous glucose tolerance tests (IVGTTs) were assessed in 41 middle-aged to older (9.1-29.5 years), socially housed, female vervets. Cluster analyses yielded four distinct IVGTT response patterns relevant...
Effects of metastable resistance training with strength and balance requirements compared to traditional resistance and balance training on cognitive performance in older adults: a randomized controlled trial
CONCLUSIONS: In contrast to BT, MRT appears to selectively enhance cognitive functions requiring inhibitory control and perceptual processing in older adults. Consequently, metabolic demands associated with MRT may offer additional cognitive benefits beyond the coordinative demands offered by traditional balance training.
Slowing down to take it in: Endocytosis during cellular aging
Aging cells functionally decline and accumulate damage through poorly understood mechanisms. In this issue, Antentor et al. (https://doi.org/10.1083/jcb.202412064) find that increased vacuolar pH in older yeast cells slows clathrin-mediated endocytosis. These findings have broad implications in aging-related plasma membrane protein quality control.
1275-nm Photobiomodulation Alleviates Brain Drainage Impairment as a Promising Therapeutic Strategy for Aging-Related Neurological Decline
Aging imposes a significant socioeconomic and healthcare burden worldwide, while effective therapy is still lacking. Impaired brain drainage and excessive accumulation of metabolites and toxins such as advanced glycation end products (AGEs) are characteristics of aging that contribute to the development of neurological disorders. Recent discoveries have highlighted the role of meningeal lymphatic vessels (MLVs) in the clearance of toxic metabolites, cells, tumors, and viruses from the brain,...
The autophagy-recessive tissue hormone DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) contributes to the pathogenesis of osteoarthritis
Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability in the elderly, characterized by the progressive destruction of cartilage, synovial inflammation, and subchondral bone remodeling. While mechanical stress, metabolic derangements, and systemic inflammation are recognized contributors, accumulating evidence underscores the pivotal role of impaired macroautophagy/autophagy in disease pathogenesis. Autophagy declines with age, depriving chondrocytes and...
Glycation-lowering compounds inhibit ghrelin signaling to reduce food intake, lower insulin resistance, and extend lifespan
Non-enzymatic reactions in glycolysis produce methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity, diabetes, and aging-associated pathologies. A combination of nicotinamide, α-lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low) lowers the deleterious effects of glycation by reducing MGO and the MGO-derived AGE, MG-H1, in mice. Gly-Low supplementation in the diet reduces food consumption, decreases body weight...
Aging and Longevity: Latest results from PubMed
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