Aging & Longevity

Engineered gene circuits often degrade due to mutation and selection, limiting their long-term utility. Here we present designs for genetic controllers which maintain synthetic gene expression over time. Using a multi-scale "host-aware" computational framework, which captures interactions between host and circuit expression, mutation, and mutant competition, we evaluate several controller architectures based on three metrics for evolutionary stability: total protein output, duration of stable...

Pulsed electromagnetic fields (PEMFs) enhance bone formation to combat osteoporosis, yet the mechanisms by which they promote bone health during aging remain unclear. This study shows PEMFs enhance new bone formation and innervation, promoting osteogenesis and reducing adipogenesis in mesenchymal stem cells (MSCs) in aging male mice. PEMF-induced osteogenesis is impaired by sensory nerve dysfunction in this model. Mechanistically, PEMFs stimulate sensory nerves to secrete semaphorin 3A (Sema3A),...

Age-related structural brain changes may be better captured by assessing complex spatial geometric differences rather than isolated changes to individual regions. We applied an analytic method to quantify age-related changes to the spatial anatomy of the brain by measuring expansion and compression of global brain shape and the distance between cross-hemisphere homologous regions. To test how global brain shape and regional distances are affected by aging, we analyzed 2603 structural MRIs...

Biomolecular condensates enable the coordination of cellular activities with high spatiotemporal selectivity. Many techniques have been developed to characterize protein condensate. However, direct visualization of protein structure in phase-separated condensate remains underexplored. Here we develop in situ quantitative imaging of secondary structure in protein condensates by stimulated Raman scattering (SRS) microscopy. Characteristic spectra of four secondary structures are obtained from...

Aging is associated with metabolic dysfunction and cardiovascular abnormalities. Defective nicotinamide adenine dinucleotide (NAD^(+)) biosynthesis correlates with aging and aging-associated complications. However, the precise molecular mechanisms linking aging-associated NAD^(+) deficiency to cardiometabolic dysfunction remain unclear. Herein, we examined whether nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD^(+) biosynthesis, influences vascular endothelial function and...

Senescent cells are known to contribute to aging and age-related diseases. One key way they influence aging is by secreting senescence-associated secretory phenotype (SASP) factors along with several damage-associated molecular pattern (DAMP) molecules. Consequently, inhibiting SASP and DAMP signaling (senomorphics) has emerged as a therapeutic strategy. Urolithin A (UA), a gut-derived metabolite produced from ellagitannins and ellagic acid found in berries, nuts, and pomegranates, has...

Polycomb group (PcG) proteins form chromatin modifying complexes that stably repress lineage- or context-specific genes in animals, plants, and some fungi. Polycomb Repressive Complex 2 (PRC2) catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) to assemble repressive chromatin. In the model fungus Neurospora crassa, H3K27me3 deposition is regulated by the H3K36 methyltransferase ASH1 and components of constitutive heterochromatin including the H3K9me3-binding protein HETEROCHROMATIN...

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CONCLUSIONS: CPIC Level A pharmacogenetic biomarkers are prevalent in Chinese older adults, with over 40% exposed to actionable gene-drug pairs and 36.5% requiring dose adjustments. These findings highlight the clinical imperative to integrate pharmacogenetic testing into geriatric care, prioritize CYP2C19 and SLCO1B1 testing, and develop region-specific guidelines to mitigate polypharmacy risks. Policymakers and clinicians should consider targeted implementation strategies to optimize...

The concept of resilience can be used to explain why there are differences in the degree to which the brain functions of different individuals are impaired due to aging and pathological factors associated with neurodegenerative diseases. It encompasses cognitive reserve, brain reserve, and brain maintenance. Long-term research has identified a default mode network (DMN) related to cognitive reserve. This mode can modulate the negative impact of Alzheimer's disease (AD) pathological burden on...

In the context of increasing life expectancy, a higher prevalence of age-related chronic diseases is becoming more common in the health landscape, many of which are closely linked to insufficient physical exercise during lifespan. On the other hand, aging is also associated with damage to various molecules, including DNA, by reactive oxygen species. Given that both senescence and muscle mass loss are intimately linked to increased levels of DNA damage and deterioration of antioxidant defense,...

CONCLUSIONS: Our findings provided a novel global perspective on the temporal trends of PAH burden in the elderly population, augmenting the existing evidence and understanding of PAH epidemiology in this demographic. Additionally, these results identify gaps in various aspects of prevention, management, and intervention strategies for PAH in the elderly.

Aging represents a major risk for human neurodegenerative disorders, such as dementia and Alzheimer's disease, and is associated with a functional decline in neurons and impaired synaptic plasticity, leading to a gradual decline in memory. Previous research has identified molecular and functional changes associated with aging through transcriptomic studies and neuronal excitability measurements, while the role of chromatin-level regulation in vulnerability to aging-related diseases is not well...

CONCLUSION: Findings suggest the need for targeted interventions that take into account sociodemographic and psychological factors to support the safe use of medications in aging societies.

CONCLUSIONS: This study underscores the need for ACPbp in RACFs, provides guidelines for such programs and identifies the specific aspects necessary for the development of ACPbp programs in this context.

CONCLUSION: This study revealed that anemia is prevalent among individuals aged ≥ 60 years in China and is related to age, residence type, hypoproliferation, hematocrit, total cholesterol and the creatinine clearance rate. Research has also confirmed that anemia is associated with worse overall survival in Chinese older adults.

Fibroblasts, critical for skin structure and function via extracellular matrix (ECM) production, undergo senescence linked to ECM changes and inflammation via senescence-associated secretory phenotypes (SASPs). Transforming growth factor (TGF-β), a pleiotropic cytokine, modulates fibroblast function through multiple signaling pathways, inducing cell cycle arrest, oxidative stress, DNA damage, and SASP production. These processes disrupt ECM homeostasis, exacerbate inflammation, and impair tissue...

Circadian time keeping system (CTS) consisting of network of central and peripheral clocks regulates physiological, metabolic, and behavioural processes in alignment with the 24 hour. Desynchrony between central and peripheral clocks contributes to the pathogenesis of age-related conditions such as metabolic syndrome, cognitive decline, immune dysfunction, and neurodegenerative diseases etc. Sex-specific susceptibilities further modulate circadian resilience, with hormonal changes and redox...

CONCLUSIONS: The 6-month Exernet-Elder 3.0 training programme demonstrated an ICER of €115 per SPPB point gained, €407 per point of frailty reduction, and €6274 per QALY gained. The intervention was low-cost (€164 per participant) and produced clinically meaningful improvements in functional capacity, HRQoL, and frailty. These findings underscore the importance of integrating a structured, group-based exercise programmes into public health strategies to address the growing socioeconomic and...

Lung cancer is a leading cause of cancer-related mortality worldwide and is predominantly diagnosed in older adults, underscoring the need to explore aging-related biological mechanisms that influence disease progression and prognosis. Cellular senescence, a hallmark of aging, plays a dual role in cancer by contributing to both tumor suppression and tumor promotion through its influence on tumor growth, modulation of the tumor microenvironment, the senescence-associated secretory phenotype...