Aging & Longevity
A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation
The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal...
Pancreatic beta-Cell Remodeling in Health and Aging: Lessons from Rodents and Humans
Pancreatic β-cells are essential for maintaining glucose homeostasis throughout life. Although rodent models have been instrumental in elucidating β-cell biology, notable differences exist between rodents and humans across fetal, postnatal and adult stages. This review provides a comparative analysis of β-cell development, proliferation and regenerative capacity between these two species, highlighting critical divergences that must be considered when translating preclinical findings to human...
Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases
Heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations are key drivers of mitochondrial diseases, yet their tissue-specific and cell-specific accumulation patterns during aging and the mechanistic links to pathology remain poorly understood. In this study, we employed DddA-derived cytosine base editor technology to generate three mouse models harboring distinct pathogenic mitochondrial tRNA mutations. These mutations exhibited age-dependent accumulation in the kidneys, leading to severe...
Senescent macrophages induce ferroptosis in skeletal muscle and accelerate osteoarthritis-related muscle atrophy
Muscle atrophy around joints is a common issue for people with osteoarthritis (OA), but its causes are poorly understood. Here we demonstrate that chronic inflammation in quadriceps muscle coincides with OA in mice, characterized by an increase in macrophages, activation of inflammatory pathways and tissue vascularization. We show that, during OA progression, macrophages progressively exhibit increasing phenotypes of senescence and promote muscle atrophy through paracrine induction of...
Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells
RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5'...
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...
Aging and Longevity: Latest results from PubMed
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