Aging & Longevity
The emerging role of dysregulated propionate metabolism and methylmalonic acid in metabolic disease, aging, and cancer
Propionate metabolism dysregulation has emerged as a source of metabolic health alterations linked to aging, cardiovascular and renal diseases, obesity and diabetes, and cancer. This is supported by several large cohort population studies and recent work revealing its role in cancer progression. Mutations in several enzymes of this metabolic pathway are associated with devastating inborn errors of metabolism, resulting in severe methylmalonic and propionic acidemias. Beyond these rare diseases,...
Metformin delays the decline in thermogenic function of brown adipose tissue in a mouse model of Hutchinson-Gilford progeria syndrome
Brown adipose tissue (BAT) is the primary site for non-shivering thermogenesis in the body and plays a crucial role in maintaining core body temperature. However, its function gradually declines with age. To mitigate the age-related decline in BAT thermogenic capacity, we treated progeroid mice with metformin to investigate the potential mechanisms by which metformin can slow the reduction in BAT thermogenic function. We found that progeroid mice, after receiving metformin treatment, showed...
Rhythms and shifts of chemokines and cytokines interplay in a decade lifespan: The longitudinal community-based Bambui health and aging study
Aging is associated with several physiological changes, including a remarkable remodeling of the immune system. Herein, the rhythms and shifts in serum immune mediators were characterized in a decade lifespan as a longitudinal community-based prospective investigation from Bambuí Health and Aging Study. The study population included paired samples from 713 subjects survivors from the original BHAS cohort and at 10-years Follow-up, categorized into 5-years age range intervals (60-64^(Yrs) towards...
Halt aging? - functional HSCs lead the way
No abstract
Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging
Aging leads to progressive decline in organ and tissue integrity and function, partly due to loss of proteostasis and autophagy malfunctioning. A decrease with age in chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation, has been reported in various organs and cells from rodents and humans. Disruption of CMA recapitulates features of aging, whereas activating CMA in mice protects against age-related diseases such as Alzheimer's, retinal degeneration and/or...
Multiomics atlas reveals molecular and genetic drivers of human ovarian aging
No abstract
Stability of locus coeruleus cell counts despite volume loss in cognitively impaired aged rhesus macaques
The locus coeruleus (LC) is a brainstem nucleus that provides the primary source of noradrenaline (NA) in the nervous system and optimizes behavioral performance in mammals. In humans, the LC shows Alzheimer's disease (AD)-like pathology at its earliest stages, but little is known about LC integrity in normative, non-pathological aging. The present research addresses these gaps by investigating neuron numbers, densities of glia and vasculature, and volume of the LC itself in cognitively assessed...
Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice
Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific...
Elderly vulnerability to temperature-related mortality risks in China
The elderly face elevated mortality risk due to rising temperature. Previous assessments of temperature-related mortality, however, lack a comprehensive analysis of distinct impacts of temperature change across different timescales and characteristics. Using a longitudinal survey of 27,233 elderly Chinese citizens from 2005 to 2018, we establish connections between rising temperatures, temperature variability, and extreme heat with increased mortality risk, assessed through four annual metrics...
Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance and male germ cell survival
The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGOs) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the...
Associations of Accelerometer-Measured Physical Activity With Dementia, Anxiety, and Depression Among Older Adults
CONCLUSIONS: Higher and increasing MVPA over time is associated with better neuropsychiatric health in individuals aged ≥ 70 years. Future studies should prioritize evaluating detailed PA trajectories to better understand how different doses, intensities, and modalities of PA impact neuropsychiatric decline in older adults.
Around the EQUATOR With Clin-STAR: AI-Based Randomized Controlled Trial Challenges and Opportunities in Aging Research
The CONSORT 2010 statement is a guideline that provides an evidence-based checklist of minimum reporting standards for randomized trials. With the rapid growth of Artificial Intelligence (AI) based interventions in the past 10 years, the CONSORT-AI extension was created in 2020 to provide guidelines for AI-based randomized controlled trials (RCT). The Clin-STAR "Around the EQUATOR" series features existing reported standards while also highlighting the inherent complexities of research involving...
Microbiota from young mice counteracts susceptibility to age-related gout through modulating butyric acid levels in aged mice
Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a...
Associations between lifestyle factors, physiological conditions, and epigenetic age acceleration in an Asian population
Epigenetic clocks use DNA methylation (DNAm) levels to predict an individual's biological age. However, relationships between lifestyle/biomarkers and epigenetic age acceleration (EAA) in Asian populations remain unknown. We here explored associations between lifestyle factors, physiological conditions, and epigenetic markers, including HannumEAA, IEAA, PhenoEAA, GrimEAA, DunedinPACE, DNAm-based smoking pack-years (DNAmPACKYRS), and DNAm plasminogen activator inhibitor 1 level (DNAmPAI1). A...
The interplay of p16INK4a and non-coding RNAs: bridging cellular senescence, aging, and cancer
p16INK4a is a crucial tumor suppressor and regulator of cellular senescence, forming a molecular bridge between aging and cancer. Dysregulated p16INK4a expression is linked to both premature aging and cancer progression, where non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs) play key roles in modulating its function. These ncRNAs interact with p16INK4a through complex post-transcriptional and epigenetic mechanisms,...
Investigating the aging-modulatory mechanism of Rasayana Churna, an Ayurvedic herbal formulation, using a computational approach
This study investigates the impact and mechanisms of Rasayana Churna, an Ayurvedic poly-herbal formulation, in treating aging-related disorders through text mining, network pharmacology, molecular docking simulation, Super-MMPBSA, and density functional theory. The text mining of Rasayana Churna highlighted the diverse therapeutic potential of Phyllanthus emblica, Tinospora cordifolia, and Tribulus terrestris in managing aging-related disorders through their antidiabetic, antioxidant, and...
Disturbances in cell wall biogenesis as a key factor in the replicative aging of budding yeast
Aging is a multifactorial process that significantly impairs organismal function. Yeast is one of the model organisms used in aging research. Our understanding of the impact of the cell wall on aging remains elusive. Yeast cell wall is a complex and dynamic structure that plays a crucial role in the growth, survival, and aging of Saccharomyces cerevisiae. In this study, we demonstrated for the first time that the deletion of genes involved in cell wall biogenesis leads to significant impact on...
Neuroinflammaging and the Immune Landscape: The Role of Autophagy and Senescence in Aging Brain
Neuroinflammation is closely linked to aging, which damages the structure and function of the brain. It is caused by the intricate interactions of immune cells in the aged brain, such as the dysregulated glial cells and the dysfunctional astrocytes. Aging-associated chronic low inflammation, referred to as neuroinflammaging, shows an upregulated proinflammatory response. Autophagy and senescence play crucial roles as moderators of aging and neuroinflammatory responses. The dysregulated...
Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice
Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their...
A cohort study reveals shared and distinct serum metabolic biomarkers for major adverse cardiovascular events in middle-aged and older adults
We assessed the association of serum metabolites with the occurrence of major adverse cardiovascular events (MACE) in middle-aged and elderly individuals, explored the value of metabolomics in predicting MACE, and compared the distinctions in MACE risk-related metabolic biomarkers between middle-aged and elderly groups. Among the participants of the UK Biobank who underwent baseline assessment through nuclear magnetic resonance (NMR)-based metabolomic profiling of 168 serum metabolites and had...
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