Aging & Longevity
Stem cell therapies for diabetes
Diabetes has long-term, potentially severe implications for healthspan and lifespan and imposes an immense burden on global healthcare, the economy and society. Although a repertoire of medications is available to treat diabetes, these do not properly address the eventual lack of functional pancreatic beta cells that are needed to secrete insulin and maintain glucose homeostasis. Human islet cell transplantation from deceased donors is an established treatment for insulin-requiring type 1...
Cholesterol's hidden impact: the nonlinear link between remnant cholesterol (RC) and phenotypic age acceleration (PhenoAgeAccel)
Cholesterol metabolism disorders have been shown to correlate with multiple physiopathologic aspects of cellular aging. However, whether indicators reflecting cholesterol metabolism [e.g., remnant cholesterol (RC)] can serve as biomarkers for biological aging remains unclear. To address this gap, this study aimed to explore the relationship between RC and phenotypic age acceleration (PhenoAgeAccel) using data from the National Health and Nutrition Examination Survey (NHANES) database. First,...
Acute corticospinal and reticulospinal responses to strength training in ageing
Ageing is associated with declines in neuromuscular function, yet the neural mechanisms underlying strength adaptations in older adults remain unclear. While the corticospinal tract (CST) is the primary pathway for voluntary movement, the reticulospinal tract (RST) may play a compensatory role with age. This study investigated CST and RST responses following a single session of high-intensity metronome-paced strength training (MPST) in young and older adults. Thirty-five participants (17 young,...
A reference model of circulating hematopoietic stem cells across the lifespan with applications to diagnostics
With aging, deviation of human blood counts from their normal range accompanies the transition from health to disease. Hematopoietic stem and progenitor cells (HSPCs) deliver life-long multi-lineage output, but their variation across healthy humans with aging, and their diagnostic utility, haven't been characterized in depth thus far. To address this, we introduced an HSPC reference model using single-cell RNA profiling of circulating CD34^(+) HSPCs from 148 healthy age- and sex-diverse...
Mixed surfactants for stabilizing and controlling water transport in double emulsions
Double emulsions, comprising an aqueous droplet enclosed within an oil shell, hold great potential as versatile microcompartments for a variety of applications. However, their widespread utility is often limited by inherent instability and uncontrolled water transport. In this study, we use droplet microfluidics to prepare double emulsions with uniform thin oil shells stabilized by mixed surfactant systems. By combining monomeric and polymeric surfactants, we demonstrate that polymeric...
Circadian clock and its effect on aging and lifespan
The circadian clocks of the cell orchestrate a daily transcriptional rhythm that schedules key activities of the cell to maintain homeostasis and support resilience. Circadian rhythm is driven by the periodic oscillations of transcriptional activators and translational repressors, occurring in both the central and peripheral clocks. Accumulating evidence shows that aging impairs the functional synchrony of the circadian system which further escalate age-related disorders. In addition, the...
Deep learning predicts onset acceleration of 38 age-associated diseases from blood and body composition biomarkers in the UK Biobank
A major challenge in multimorbid aging is understanding how diseases co-occur and identifying high-risk groups for accelerated disease development, but to date associations in the relative onset acceleration of disease diagnoses have not been used to characterize disease patterns. This study presents the development and evaluation of a neural network Cox model for predicting onset acceleration risk for age-associated conditions, using demographic, anthropomorphic, imaging, and blood biomarker...
PCSK9 expression and cancer survival: a prognostic biomarker at the intersection of oncology and geroscience
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in cholesterol metabolism; however, emerging evidence suggests it plays a broader role in the regulation of cellular aging mechanisms and the pathogenesis of age-related diseases. Given that cancer is an age-related disease, PCSK9 has garnered attention for its potential impact on tumor progression and patient survival. In this study, we conducted a comprehensive analysis of PCSK9 expression across...
Improving Care for Those Living With Serious Illnesses and Individuals Approaching End of Life: A Decade of Investments
CONCLUSIONS: This assessment highlights JAHF's role of catalyst, collaborator, and convener. JAHF's approach to grantmaking-including mission alignment, commitment, flexibility, active engagement, and focus on collaboration-contributed to the impact achieved by grantees.
Correction to "Multiple Outcomes of the Germline p16(INK4a) Mutation Affecting Senescence and Immunity in Human Skin"
No abstract
Microbiological Foundations to Optimise Intrinsic Capacity and Promote Healthy Ageing: An Integration Into the Life Course Approach
The World Health Organization (WHO) defines healthy ageing as the process of developing and maintaining functional ability, comprising an individual's intrinsic capacity, the environment and the interaction of the two. The framework is based on a positive approach to ageing, giving value to the resources individuals can rely upon as they age and that they can build their physical, mental and social health, and overall well-being. To promote healthy ageing, it is important to understand better...
Reliability and validity of the Clinical pHysical rEsilience assEssment Scale (CHEES) in community-dwelling older adults
CONCLUSIONS: The CHEES exhibits good reliability and validity; therefore, it can be used as a reliable tool for evaluating the physical resilience of older adults in community settings.
Can a pill replace exercise? Swigging this molecule gives mice benefits of working out
No abstract
A host organelle integrates stolen chloroplasts for animal photosynthesis
Eukaryotic life evolved over a billion years ago when ancient cells engulfed and integrated prokaryotes to become modern mitochondria and chloroplasts. Sacoglossan "solar-powered" sea slugs possess the ability to acquire organelles within a single lifetime by selectively retaining consumed chloroplasts that remain photosynthetically active for nearly a year. The mechanism for this "animal photosynthesis" remains unknown. Here, we discovered that foreign chloroplasts are housed within novel,...
Systematic profiling reveals betaine as an exercise mimetic for geroprotection
Exercise has well-established health benefits, yet its molecular underpinnings remain incompletely understood. We conducted an integrated multi-omics analysis to compare the effects of acute vs. long-term exercise in healthy males. Acute exercise induced transient responses, whereas repeated exercise triggered adaptive changes, notably reducing cellular senescence and inflammation and enhancing betaine metabolism. Exercise-driven betaine enrichment, partly mediated by renal biosynthesis, exerts...
Cellular senescence in chronic obstructive pulmonary disease: Molecular mechanisms and therapeutic interventions
Chronic obstructive pulmonary disease (COPD) is the world's fourth highest reason for mortality, accounting for 3.5 million deaths in 2021, and about 5 % of total global deaths. Emphysema and chronic bronchitis are the two major pathologies of COPD. Tobacco smoke, dust, vapors, and fumes, outdoor air pollutants, genetic factors, ageing, infections, and asthma are the risk factors of COPD. On the other hand, senescence is permanent halt in cell cycle accompanied by phenotypic alterations due to...
A lysosomal surveillance response to stress extends healthspan
Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H^(+)-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive...
Overexpression of the Dicer family genes influences lifespan and stress resistance in a tissue-, sex-, and stressor-specific manner in Drosophila melanogaster
Small non-coding RNAs coordinate essential cellular processes, including gene expression regulation, genome stability maintenance, and transposon suppression. These processes determine aging, lifespan, and resistance of cells and organisms to stress. In this work, we conducted a comprehensive study of the geroprotective effects of overexpression of two Dicer family genes (Dcr-1 and Dcr-2, which are responsible for the biogenesis of miRNAs and siRNAs) in different tissues of Drosophila...
A Dock8-dependent mechanosensitive central actin pool maintains T cell shape and protects nucleus during migration
Immune cells navigate through complex tissue architectures by extensive cellular deformation, low adhesion, and high cell velocities. Loss-of-function mutations in Dedicator of Cytokinesis 8 (Dock8) are associated with immunodeficiency as immune cells becoming entangled during migration through dense environments, but their migration on two-dimensional surfaces remains entirely intact. Here we investigated the specific cytoskeletal defect of Dock8-deficient activated T cells and describe a...
Identifying the target, mechanism, and agonist of alpha-ketoglutaric acid in delaying mesenchymal stem cell senescence
α-ketoglutaric acid (AKG), a tricarboxylic acid cycle metabolite central to aerobic metabolism and longevity, retains unresolved anti-aging protein targets. Here, we demonstrate that reduced isocitrate dehydrogenase 1 (IDH1) expression during senescence lowers AKG production, accelerating the aging of mesenchymal stem cells (MSCs). Exogenous AKG or IDH1 overexpression restores AKG levels, enabling 2-oxoglutarate and Fe(II)-dependent oxygenase domain-containing protein 1 (OGFOD1)-catalyzed...
Aging and Longevity: Latest results from PubMed
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