Aging & Longevity

Changes in brain [NADPH]/[NADP^(+)] and [NAD^(+)]/[NADH] may contribute to aging. Anti-aging dietary restriction (DR) and intermittent fasting (IF) alter redox states that may contribute to their longevity effects. Pyruvate/lactate and acetoacetate/beta-hydroxybutyrate are indicators of the cytoplasmic and mitochondrial [NAD^(+)]/[NADH], respectively, while the malate/pyruvate and isocitrate/alpha-ketoglutarate are indicators of the cytoplasmic [NADPH]/[NADP^(+)]. Using these metabolite-pair...

Most diseases are not caused by large-effect single factors but by the cumulative impact of small, context-dependent perturbations arising from genetic variants, personal behavior, or environmental exposures, a phenomenon we term the "long tail" of biology. Early disease signals often differ from late-stage biomarkers and evolve across demographic, lifestyle, and environmental contexts. Shifting medicine from reactive treatment to proactive health requires detecting and interpreting these...

Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive...

Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse...

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CONCLUSIONS: The LTC Data Cooperative offers novel EHR data capturing clinical measures not available in the Minimum Data Set or claims data on a SNF resident population that is comparable to the national population. Studies using these data can generate evidence to inform and improve clinical care and outcomes for older adults in the SNF setting.

Mixed-matrix membranes (MMMs) with high chain packing density by incorporating soluble macrocycle compounds represent a promising class of materials for gas separation. However, achieving the ultra-high selectivity (He/CH(4) > 1000) for helium extraction from natural gas with ultra-low helium content remains a formidable challenge, especially for Matrimid membranes, which are commercially available but exhibit relatively low permeability and moderate selectivity. Herein, the cyclic Cyclen with...

Aging is accompanied by progressive impairment of neurovascular coupling (NVC), the mechanism that matches local cerebral blood flow to neuronal activity, contributing to cognitive decline and the development of vascular cognitive impairment and dementia. Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore NVC in aged mice, suggesting that circulating factors can rejuvenate cerebrovascular function. Yet, the molecular mediators responsible for this...

Subjective and objective markers are important in describing healthy aging, yet little is known about their relationships. This study analysed the time-dependent association of dehydroepiandrosterone sulfate (DHEAS) with subjective health. At baseline, DHEAS was measured in participants aged 45-83 randomly selected from the general population. Subjective mental and physical health were assessed using the 12-item Short Form (SF-12) questionnaire at baseline and two follow-ups. In sex-specific...

Dietary restriction may extend lifespan by improving late-life gut health. Because micronutrients mediate the effects of macronutrient ratios on longevity, we examined how cholesterol limitation affects gut health in female Drosophila melanogaster. Low-cholesterol diets increased intestinal permeability and reduced lifespan, however, not all flies lost barrier function before dying. This indicates gut dysfunction is either a marker of ageing, or contributes to death, but predominantly during...

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder whose progression is closely associated with time. However, most diagnostic models are based on single time-point data, overlooking longitudinal disease characteristics. Structural magnetic resonance imaging (sMRI) has been widely utilized in the study of AD. To address the need for multi-time series analysis in longitudinal AD research and the integration of features from different brain tissues, we propose a Multi-Branch...

Visceral adipose tissue (VAT) is increasingly recognized as a metabolically active organ that contributes to systemic metabolic dysfunction and aging. Accumulation of VAT is thought not merely to be a biomarker of but also a causal contributor to impaired metabolic health and reduced lifespan. In this Review, we summarize evidence from both animal and human studies to evaluate whether this causal relationship truly holds. Our assessment indicates that VAT is not inherently harmful; rather, its...

Oxidative stress contributes to age-related musculoskeletal decline, partly through disruption of glutathione-dependent redox homeostasis. Although creatine and β-hydroxy-β-methylbutyrate (HMB) have been individually linked to antioxidant and cytoprotective effects, their combined influence on systemic redox balance in older adults remains insufficiently characterized.To examine the effects of creatine plus HMB supplementation on oxidative stress biomarkers and composite redox indices, and to...

Blood levels of neurofilament light chain (NfL) increase with age in healthy humans and have been shown to predict all-cause human mortality. To determine whether this relationship is conserved across species, we analyzed NfL in the blood of various animals. We observed age-related increases in NfL levels comparable to those seen in humans in mice, cats, dogs and horses. Longitudinal analysis of NfL trajectories in aged mice demonstrated that a faster rate of NfL increase predicts mortality....

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Many non-model rodent species are inaccessible to genetic engineering due to our limited understanding of their reproductive biology. Here, we present a low-cost, camera-based estrous-tracking technology that enables transgenesis in the white-footed mouse Peromyscus leucopus, a key reservoir for Lyme disease. We demonstrate the efficient generation of pregnant and pseudopregnant mice via timed ovulation, provide protocols for embryo generation, cultivation, microinjection, and transplantation as...

Endothelial cells (ECs) are key metabolic gatekeepers, yet their role in metabolic health remains unclear. Given their central involvement in energy metabolism, mitochondria are ideally positioned to enable ECs to adapt to ever-changing metabolic requirements. Here, we explore the hypothesis that mitochondrial dynamics proteins in ECs influence whole-body metabolic status. Genetic deficiency of Mfn2 in ECs (Mfn2^(iΔEC)), but not of Mfn1^(iΔEC), induces a mitohormetic response in the adipose...

The behavioral aspects of aging in the domestic dog have primarily been investigated through owner-reported scales that measure specific behavioral signs of aging, and laboratory-based memory and cognitive tests. We need to know more about how aging affects everyday behavior and functionality in owned dogs. This study tested a methodology for identifying patterns in everyday physical and behavioral function associated with behavioral tests and scales. Fifty-seven family dogs aged 8+ years were...

Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity...

Skeletal muscle aging causes loss of both muscle mss and strength, often leading to sarcopenia. Clinical manifestation of sarcopenia has been found to improve with exercise intervention. The molecular mechanisms in response to exercise intervention in aged skeletal muscles are not fully understood. We performed transcriptomic profiling of aged animal model with exercise intervention for identifying the plausible mechanism leading to enhanced muscle function. Expression levels of 43,629 RNAs were...