Aging & Longevity
Metformin improves cardiac stress tolerance and mitochondrial function during early aging
Cardiac aging reduces stress resistance and increases the susceptibility to myocardial injury. Although cardiac dysfunction typically manifests in late-stage aging, the underlying process begins in middle age. Elevated endoplasmic reticulum (ER) stress is a key contributor to cardiac aging. We have shown that ER stress increases in middle-aged hearts and peaks in advanced age, while chronic metformin treatment reduces ER stress and improves mitochondrial function in late-aged hearts. This study...
Real-time visualization of collagen assembly uncovers metastable properties in hierarchical organization
Collagen, a central component of the extracellular matrix (ECM), precisely regulates tissue mechanical properties and biological functions through hierarchical assembly, playing a vital role in maintaining homeostasis. However, the molecular mechanism of assembly remains poorly understood, limiting insights into tissue remodeling, aging, and ECM-related diseases. Here, we employ time-resolved cryo-electron microscopy to resolve two critical hierarchical intermediates in fibrillar collagen...
Reactivating dead sodium for durable and high-rate anode-free sodium batteries
Reactivating dead alkali metal is an effective strategy for extending the lifespan of alkali metal batteries. Until now, relevant works are mainly concentrated in lithium batteries, however, the reactivation of dead Na remains a mystery. Herein, dead Na reactivation is realized by a reverse-pulse-interspersed charging strategy. Transient large reverse currents are incorporated into the battery charging protocol, during which dead Na can be reactivated by the dielectrophoresis effect. Different...
Clinical response to systemic AAV gene therapy in a large animal model of late-stage lysosomal storage disease
The benefit of early diagnosis and treatment has been demonstrated in animal models of several lysosomal storage diseases. In a clinical setting, however, diagnoses are often not made until after patients become symptomatic. The lysosomal storage disease alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions throughout the brain and other tissues. In a feline model of alpha-mannosidosis, we previously...
The aging extracellular matrix as a missing link in senescent cell accumulation and persistence
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Mitigating the Hawthorne effect in aging research
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Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1
Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in multiple cancers and critically contributes to systemic methionine accumulation. However, the structural basis of LAT4 function remains poorly understood, and no effective inhibitors have been developed to date. In this study, we present high-resolution cryo-electron microscopy structures of LAT4 and the...
Frequency-specific photobiomodulation at theta and gamma enhances cognitive networks and mitigates age-related decline
Photobiomodulation (PBM) is a non-invasive strategy to enhance cognitive function, yet the effects of stimulation frequency remain unclear. We applied pulsed 810 nm PBM at 5 Hz or 40 Hz to the frontal cortex of adult rats, and 40 Hz PBM to aged rats. In young adults, both stimulation frequencies enhanced cognitive flexibility, and in aged rats 40 Hz PBM improved learning speed. In terms of brain changes, we studied cytochrome c oxidase (CCO) activity, c-Fos expression and protein levels. We...
Correlations between white matter hyperintensities, magnetic resonance imaging findings, and cognition in the oldest old: a multimodal cross-sectional study
Small vessel disease and brain atrophy are linked to cognition in later life, but whether these associations persist in the oldest old is unclear, as lesion burden and survivorship may change effect sizes. We analyzed 249 adults aged 89-94 years from the Kawasaki Aging and Wellbeing Project. White matter hyperintensities (WMHs) were segmented on fluid-attenuated inversion recovery; gray and white matter volumes were derived from T1-weighted magnetic resonance imaging; and peak width of...
Falls and functional fitness among older adults in Sub-Saharan Africa: findings from the first population-based cross-sectional study in Ghana
CONCLUSION: Falls are common among older adults in Ghana, with risk influenced by sex, residence, and functional status. Functional fitness plays a central role in fall risk, underscoring the value of targeted interventions to promote safe and healthy ageing in sub-Saharan Africa.
Peripheral Artery Disease, Aging, and Falls: Forecasting a Looming Challenge for Older Adults
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Short-term hearing aid use reduces auditory cortical responses to speech-in-noise listening among older adults with age-related hearing loss
Age-related hearing loss (ARHL) is an increasingly common feature of aging and has been linked to poorer psychosocial wellbeing and increased dementia risk. Individuals with ARHL experience speech perception difficulties in noisy environments, wherein the brain must "turn up the volume" or upregulate neural activity to accurately parse speech from background noise. As the aging population steadily increases worldwide, it is essential to develop effective, non-invasive, and easily attainable...
Myofascial pain in older adults: a geroscience-informed framework integrating precision geriatrics and digital therapeutics
Myofascial pain syndrome (MPS) in the elderly is a significant contributor to chronic pain and functional decline, driven by a unique set of age-related pathophysiological challenges. Core geroscience principles-including sarcopenia, inflammaging, and cellular senescence-converge to create a state of heightened central sensitization that amplifies pain. Traditional pharmacotherapy is fraught with risks in this population due to polypharmacy and vulnerability to adverse effects, with many common...
Studying neurocognitive systems for sustained attention in neurogeriatric patients: protocol of the SENSE-AGE study
BACKGROUND: Sustained attention is a complex cognitive function required for the successful performance of tasks such as walking, cycling, driving, conversations and other prolonged tasks. Deficits of this function are associated with frailty, falls, and general cognitive decline in older adults. Sustained attention declines with age and is impaired in many neurological disorders. However, little is known about the underlying neurophysiological characteristics of sustained attention deficits in...
Dissecting shared genetic architecture between pan-cancer and aging-related traits: a genome-wide cross-trait analysis
The association between aging and cancer has been extensively documented in observational studies, but their shared genetic basis remains unclear. Leveraging genome-wide association studies summary statistics of aging and pan-cancer (87,531 cases and 314,193 controls) within the European population, genetic correlation and Mendelian randomization analyses were used to estimate genetic correlations, and infer causal relationships between seven aging-related traits and pan-cancer. We further...
Host genetics and diet jointly shape the microbiome of Drosophila melanogaster but do not predict lifespan or age-related traits
The microbiome is a key determinant of organismal health, yet inter-individual variability and heterogeneous responses to environmental conditions complicates the understanding of its effects on hosts. Here, we present a comprehensive analysis using the Drosophila Genetic Reference Panel (DGRP) to investigate how the interplay between host genetic variation and diet influences microbiome composition, and to assess whether microbiome features in young flies can be used to predict lifespan and...
The aging eye: navigating molecular mechanisms and innovative interventions
The global demographic shift toward aging has precipitated a surge in age-related ocular pathologies, imposing a formidable public health challenge that demands urgent intervention. Blinding disorders such as age-related macular degeneration (AMD), cataracts, and dry eye disease exemplify this crisis, with their pathogenesis being intrinsically linked to tissue-specific aging processes in the eye. At the molecular level, core pathways including telomere attrition, oxidative stress, cellular...
Nitric Oxide Redox Signaling as a Convergent Mechanism in Aging and Fibrosis
Nitric oxide (NO) is a pleiotropic gaseous mediator that regulates tissue homeostasis. At physiological levels, it functions as a precise signaling molecule through soluble guanylate cyclase (sGC) activation and the reversible S-nitrosylation of cysteine residues. However, in the context of aging and fibrosis, oxidative stress disrupts this balance. The increased generation of superoxide (O₂•⁻) anions diverts NO from homeostatic signaling to form peroxynitrite (ONOO⁻), a potent oxidant. This...
Stress is inevitable; recovery is conditional: bioenergetic limits of resilience in aging and disease
Aging, stress-related disorders, and chronic disease are often examined across separate domains-stress physiology, nutrition, psychiatry, and geroscience-despite converging on shared phenotypes of functional decline and reduced resilience. Although adaptive responses to stress are well characterized, why comparable exposures yield sustained resilience in some individuals but progressive dysfunction in others remains insufficiently explained. We propose that the missing unifying constraint is not...
Association between dietary patterns and CAIDE-predicted dementia risk: A 20-year cohort of the Korean Genome and Epidemiology study
This study examined associations between dietary habits and the risk of developing Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)-predicted late-life dementia risk in Korean adults. A total of 5,042 participants aged 40-69 years were included. We assessed associations between dietary patterns-the Mediterranean diet, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, Korean Healthy Eating Index (KHEI), and Empirical Dietary Inflammatory Index...
Aging and Longevity: Latest results from PubMed
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