Aging & Longevity
Phenylalanyl-tRNA synthetase FARS-1/FARSA balances longevity and immunity by downregulating endogenous mitochondrial double-stranded RNAs
Endogenous double-stranded RNAs (dsRNAs) are immunogenic self-molecules that drive aberrant immune activation under pathological conditions. Here, we show that dsRNAs and their regulation by RNA-binding proteins are key determinants of the fine balance between aging and immunity in Caenorhabditis elegans and cultured human cells. We find elevated levels of dsRNAs with organismal aging and cellular senescence. We identify a moonlighting function for phenylalanyl-tRNA synthetase, FARS-1/FARSA, as...
Time-restricted feeding improves functional capacity of adipose-derived stem cells with activation of OSK-associated transcriptional programs
Time-restricted feeding (TRF), a circadian-based dietary intervention, has emerged as a promising strategy to counteract metabolic and age-related dysfunctions. However, how TRF can reverse stem cell aging and restore tissue regenerative potential remains unclear. In this study, we investigated the effects of long-term TRF on senescent adipose-derived stem cells (ADSCs) in a high-fat diet (HFD) induced aged mice model. Mice were assigned to standard or HFD diets under ad libitum or TRF (8 h/day)...
Transglutaminase and its role in Alzheimer's disease: focus on mitochondria, aging, defective mitophagy, synaptic degeneration, and metabolomics
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline driven by amyloid-β plaques, tau neurofibrillary tangles, and extensive neuronal loss. Emerging evidence highlights mitochondrial dysfunction, defective mitophagy, and disrupted proteostasis as pivotal events in disease progression. Transglutaminase TG2, a multifunctional calcium-dependent enzyme, has gained attention for its capacity to link these pathological processes. Beyond...
Age- and sex-dependent transcriptomic network alterations in sepsis
Sepsis arises from a dysregulated immune response to infection, causing systemic inflammation and high mortality. Its nonspecific symptoms and complex molecular mechanisms make early diagnosis and therapeutic development challenging. The contribution of host factors to this heterogeneity is not fully understood. We investigated whether baseline gene co-expression networks are preserved or reorganized in sepsis and whether age and sex influence these networks by analyzing RNA-seq data from...
Directing intermediate phase crystallographic orientation promotes carbon-based CsPbI<sub>3</sub> perovskite solar cells to beyond 20% efficiency
Inorganic CsPbI(3) perovskite, known for its high chemical stability and near-ideal bandgap, offers a promising solution to the instability of organic-inorganic hybrid perovskites that limit perovskite solar cells (PSCs) longevity. However, the conventional intermediate phase (dimethylammonium lead iodide, DMAPbI(3)) templating method suffers from inefficient phase conversion, hindering high-performance PSC development. To overcome this limitation, we engineered the crystallographic orientation...
Life's essential 8 and longevity: the sustained impact of cardiovascular health on mortality from middle age to centenarians
While Life's Essential 8 (LE8) provides a comprehensive measure of cardiovascular health (CVH), its association with mortality among the oldest-old, including centenarians, remains unclear. This study evaluated the relationship between LE8-defined CVH and all-cause mortality across adulthood using data from the China Kadoorie Biobank (Hainan cohort) and the China Hainan Centenarian Cohort Study, including 31,473 individuals aged 30-116. Participants were categorized by life stage and CVH score...
Deprotonation suppressing via competitive proton transfer control for efficient perovskite solar cells
Despite the efficacy of the methylammonium chloride (MACl) additive strategy in stabilizing the α-phase of formamidine-based perovskite materials, a persistent and formidable challenge from the irreversible deprotonation of MA^(+) cation still bothers the fabrication of satisfactory formamidine (FA)-based perovskite photosensitive layers, thereby hindering the performance improvement of resultant perovskite solar cells. To confront this obstacle, numerous methodologies have been proposed and...
Single-cell eQTL-based Mendelian randomization identifies immune cell subtype-specific regulators of epigenetic aging and prioritizes candidate therapeutic targets
Epigenetic aging clocks offer precise measures of biological age, yet the causal contributions of immune gene expression within specific cell subtypes to epigenetic aging remain poorly understood. By integrating single-cell eQTL data from the OneK1K cohort with GWAS summary statistics for four epigenetic clocks (HannumAge Acceleration, IEAA, PhenoAge Acceleration, and GrimAge Acceleration), we performed two-sample Mendelian randomization across diverse immune cell subtypes, followed by...
Differential associations of active and passive digital modalities with health perception biases among older adults
CONCLUSIONS: The empirical correlates of the digital environment vary significantly by specific usage patterns and socioeconomic backgrounds. The digital divide extends beyond basic connectivity to include how different digital activities associate with subjective health evaluations. Recognizing that these observational correlations intertwine with lifelong personal trajectories policymakers should focus on fostering content-specific digital literacy and designing tailored digital environments...
Aging modulates amyloid clearance kinetics during anti-amyloid therapy: evidence from real-world serial amyloid PET
CONCLUSION: In this real-world cohort, aging appeared to influence the observable kinetics of amyloid reduction during anti-amyloid therapy. Early serial amyloid PET may provide useful information regarding longer-term amyloid dynamics, while baseline perfusion imaging may help identify patients with substantial downstream neurodegenerative burden who remain at risk for cognitive decline despite amyloid clearance. These findings highlight biological heterogeneity in treatment response and...
Transcranial magnetic stimulation from healthy brain aging to Alzheimer's disease: a review on mechanisms, therapeutic potential, and future clinical directions
Transcranial magnetic stimulation (TMS), a non-invasive and non-pharmacological intervention, is increasingly being explored for mitigating age-related cognitive decline and dementia. Its therapeutic potential is largely attributed to its capacity to modulate neuronal firing rates and induce neuroplastic changes and modulate neurovascular coupling within distributed neural networks that support memory, attention, and executive function. Despite growing interest, gaps remain in understanding how...
Food-chain spirochetes: a unified hypothesis for Parkinson's disease and dementia risk
Parkinson's disease (PD) and dementia have risen markedly in many regions. While aging, genetics, toxicants, and protein misfolding explain key aspects of pathology, they do not fully account for synchronized temporal trends or pronounced regional heterogeneity in recent increases. This hypothesis and theory article proposes that persistent microorganisms in industrial food systems-particularly biofilm-forming spirochetes in high-throughput poultry processing-may represent an under-recognized...
Bridging the Digital Divide: The Mediating Role of Social Engagement in Technology Use and Mental Health
ObjectivesThis study examined whether social engagement mediates the relationship between information and communication technology (ICT) use and depression and anxiety among older Americans.MethodsData came from 5,195 respondents in the 2022 National Health and Aging Trends Study. Multivariate mediation analyses were conducted using bootstrapping and Monte Carlo simulation to estimate indirect effects.ResultsCompared with non-users, ICT users showed greater social engagement and lower depression...
NMN/NAD(+) enhances SIRT2-modulated microtubule dynamics to improve mitochondrial and mitophagy functions in senescent cells
The effect of NAD^(+) in enhancing mitochondrial function and energy metabolism in human cells is closely linked to NAD^(+)-dependent sirtuins (i.e. SIRT1 and SIRT3). SIRT2 primarily functions in the cytoplasm, where it can serve as a key deacetylase for tubulin and modulates stability of microtubules. Microtubule plays a pivotal role in regulating mitochondrial dynamics, including mitochondrial movement, fission/fusion, repair, and mitophagy-dependent clearance. However, the potential role of...
Hemadyne: accordion-inspired perfusion for microphysiological systems
A crucial factor limiting the physiological relevance, reproducibility and ease of adoption of microphysiological systems is the constrained non-specific design and performance of existing perfusion systems. Inspired by the physics of the accordion music instrument, we have engineered Hemadyne, a standalone mechanical pump with compact footprint that operates without any additional instruments. The pump is paired with a custom-built control algorithm to reproduce clinical waveforms with a...
Tubular Omega-3 Fatty Acid Receptor FFAR4 Deficiency Aggravated Renal Aging and Chronic Kidney Disease
Aging leads to renal function decline and increases the risk of chronic kidney disease (CKD). Omega-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids for humans, exerting their functions via free fatty acid receptor 4 (FFAR4). Clinical studies indicate that omega-3 PUFAs supplementation shows benefits for the elderly population and CKD patients, but these results remain controversial. Herein, we found that omega-3 PUFAs alleviated renal fibrosis and tubular senescence in aged mice,...
Clin-STAR Corner: Practice Changing Advances at the Interface of Artificial Intelligence/Machine Learning and Geriatrics
Artificial intelligence (AI) methods, including machine learning (ML), are transforming healthcare by enabling personalized interventions that integrate multimodal data to support rehabilitation, preventive care, and remote monitoring. Despite their broad potential, older adults remain underrepresented in model development, raising concerns about bias and limited generalizability. As AI/ML adoption expands, it is essential to critically appraise emerging tools to ensure ethical, equitable,...
Genetic associations with longevity in a Calabrian cohort: an exploratory genome-wide study
Human longevity is a complex trait shaped by genetic background and population-specific factors. Calabria, a region in Southern Italy with a high prevalence of centenarians and relative genetic isolation, is a valuable model for investigating the genetic architecture of extreme survival. Here, we performed a genome-wide association study of longevity in 705 Calabrian individuals, comparing long-lived subjects to younger controls using a mixed-model approach that accounts for relatedness and...
The Effects of Digital Device Use on Psychological Health and Cognitive Functions in Chinese Older Adults
CONCLUSIONS: Purposeful digital engagement can improve orientation and alleviate loneliness in Chinese older adults. It also helps preserve orientation ability partly by reducing feelings of loneliness, whereas use proficiency may exacerbate loneliness and diminish life satisfaction.
Aging as the Degradation of Conjunctive Coupling: A Triadic Framework S = F E N for Biological Senescence
Despite the landmark identification of twelve hallmarks of aging (López-Otín et al., 2023), geroscience lacks a formal account of why these hallmarks interact and amplify each other, why mono-target interventions show systematically limited efficacy, and what determines the threshold at which compensatory mechanisms fail. A recent extension of the hallmarks framework has further integrated psychosocial and social determinants of aging (López-Otín & Kroemer, 2025; Kroemer et al., 2025),...
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