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Insights into DNA repeat expansions among 900,000 biobank participants

2 weeks 3 days ago
Expansions and contractions of tandem DNA repeats generate genetic variation in human populations and in human tissues. Some expanded repeats cause inherited disorders and some are also somatically unstable^(1,2). Here we analysed DNA sequencing data from over 900,000 participants in the UK Biobank and the All of Us Research Program using computational approaches to recognize, measure and learn from DNA-repeat instability. Repeats at different loci exhibited widely variable tissue-specific...
Margaux L A Hujoel

Intratumoural vaccination via checkpoint degradation-coupled antigen presentation

2 weeks 3 days ago
Decreased cross-presentation by antigen-presenting cells induces the scarcity of tumour-reactive T cells within the tumour bed, rendering in situ T cell rejuvenation through immunogenicity reprogramming highly desirable yet challenging^(1-3). Here we developed an intratumoural vaccination chimera (iVAC) to reprogram tumour cells into an antigen-presenting state (APC-like tumour cells) with restored anti-tumour immunity. The iVAC chimeras consist of a covalently engineered PD-L1 degrader...
Yu Han

Review: Systemic inflammation after stroke. Therapy and perspective

2 weeks 3 days ago
Systemic inflammation following ischemic stroke is driven by a complex interplay among pro-inflammatory cytokines, immune cell activation, and neurovascular dysfunction. Both aging and obesity significantly amplify this inflammatory response, exacerbating stroke severity and impeding recovery. Aging induces a chronic low-grade inflammatory state-referred to as inflammaging-that heightens vulnerability to stroke-induced brain injury. Similarly, obesity promotes a persistent pro-inflammatory...
Abuzan Mihaela

Evaluating the association of physical frailty with cognitive impairment: a clinical perspective in older adults of Bangladesh

2 weeks 3 days ago
CONCLUSION: The findings demonstrate a significant association between physical frailty and cognitive impairment among older adults in Bangladesh, emphasizing the role of social determinants in shaping these outcomes. The results highlight the need for targeted interventions and policy strategies addressing these determinants to promote healthy aging and mitigate cognitive decline in this population.
Nusrat E Mozid

Conserved differential expression of DDX helicase and CPEB genes in skeletal muscles potentially influences neuromuscular junctions during aging: a computational analysis

2 weeks 3 days ago
Locomotion in animals depends on muscle activity, controlled by the central nervous system. The neuromuscular junctions (NMJs) are specialized synapses pivotal in neural control of muscle function. Declining muscle function is a characteristic of aging (sarcopenia), and gradual loss of NMJ function could contribute to sarcopenia. The NMJs are cellular ensembles comprising presynaptic axon terminals, postsynaptic muscle cell, and the perisynaptic glial cells, and a coordination between these...
M J Nishanth

The microbiota-epigenome axis in healthy longevity: roles of microbial and gerobiotic metabolites - a narrative exploratory review

2 weeks 3 days ago
Aging is a dysbiotic and pro-inflammatory process that increases susceptibility to multiple chronic comorbidities. Centenarians and supercentenarians offer a unique biological model for elucidating the molecular determinants of healthy aging and exceptional longevity, as they display distinctive epigenetic signatures and a gut microbiome configuration that diverges from both younger and typically aging individuals, although substantial interindividual variability exists. The gut microbiota...
Ana Paolla Protachevicz

Aging kidney is associated with metabolic rewiring and epigenetic reprogramming

2 weeks 3 days ago
Understanding the direct connections between metabolism and chromatin dynamics may uncover potential mechanisms involved in the aging process of renal physiology. Despite known differences in incidence and aging renal disease, how biological aging intersects with renal metabolism and epigenetics in a sex-specific context remains poorly understood. Here, we determined the effect of age on renal metabolic pathways and metabolite cofactors of epigenetic modifiers in a sex-specific manner. We...
Pragney Deme

Cognitive Reserve and Its Relationship With Memory Changes: An Analysis of the Survey of Health, Aging, and Retirement in Europe (SHARE)

2 weeks 3 days ago
CONCLUSIONS: CR-related proxies were strong predictors of memory performance over the 9-year period, particularly for delayed recall. These findings reflect sociobehavioural influences associated with CR development, rather than direct evidence of CR as a neurofunctional mechanism. Promoting cognitively, socially and physically enriching activities, together with addressing depression, may help preserve memory function in aging populations.
Juan C Melendez

Age-Associated Dysregulation of Postsynaptic Mitochondria Perturbs Reinnervation Kinetics

2 weeks 3 days ago
Age-associated degeneration of neuromuscular junctions (NMJs) contributes to sarcopenia and motor function decline, yet the mechanisms that drive this dysfunction in aging remain poorly defined. Here, we demonstrate that postsynaptic mitochondria are significantly diminished in quantity in old-aged skeletal muscle, correlating with increased denervation and delayed reinnervation following nerve injury. Single-nucleus RNA sequencing before and after sciatic nerve crush from young and old-aged...
Steve D Guzman

A Machine-Learning Model of Chronological Age Based on Routine Blood Biomarkers in a Central European Population: A Potential Biological Age Marker

2 weeks 3 days ago
CONCLUSION: Using easily accessible blood biomarkers, it is possible to estimate chronological age with an MAE of 8.73 years in a large Central European population. Because the present work does not include validation against clinical outcomes, the resulting index should be regarded as a potential biological age marker. Future studies are needed to test its association with morbidity, mortality, and established biological age measures in independent cohorts.
Pavel Borsky

Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders

2 weeks 3 days ago
Oxidative stress, driven by an imbalance between oxidants and antioxidants, disrupts redox homeostasis and contributes to the development of chronic diseases, including cancer, diabetes, neurodegenerative disorders, and aging. The NRF2-KEAP1 pathway is a pivotal cellular defense mechanism against oxidative stress, regulating the transcription of cytoprotective genes. Pharmacological NRF2 activation has emerged as a promising strategy to mitigate oxidative stress-related pathologies; however,...
Ana Silva