Aging & Longevity

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease

1 year ago
Ageing is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and...
Ching-Chieh Chou

Optimization of adeno-associated viral (AAV) gene therapies vectors for balancing efficacy, longevity and safety for clinical application

1 year ago
Adeno-associated viral (AAV) vectors are an ideal platform for gene therapy due to their ability to deliver therapeutic cargos safely and effectively across various target organs. Their low immunogenicity contributes to long-lasting therapeutic effects. However, recent insights highlight the significance of CpG content within AAV vectors, where unmethylated CpG dinucleotides can trigger a TLR9-mediated immune response, leading to the rapid elimination of transduced cells. Clinical evidence...
Neel Mehta

Age and gender differences in health characteristics of older people with visual impairment

1 year ago
CONCLUSION: The prevalence of VI is high older (> 55 years) adults in Cameroon, with clear differences between men and women. The oldest individuals, and women appear to be most vulnerable. The identification of at-risk groups/persons through this cross-sectional study should make it possible to adapt public health strategies to contribute to the WHO objective of healthy ageing.
Salvatore Metanmo

Paying attention to proprioception: age affects ankle proprioception and the attentional demand of proprioceptive processing in sedentary adults

1 year ago
Ankle proprioception and attentional resources are crucial for maintaining balance and safely driving. However, research exploring the age-related integrity of ankle proprioception has yielded conflicting results, while the attentional demand of proprioceptive processing in seniors remains underexplored. We investigated how aging affects the interaction between proprioception and attention in healthy sedentary adults using a novel dual-task paradigm. Sedentary old and young adults performed an...
Marie Julie Vermette

NAT10 and <em>N</em><sup>4</sup>-acetylcytidine restrain R-loop levels and related inflammatory responses

1 year ago
N⁴-acetylcytidine (ac⁴C) is deposited on diverse RNAs by N-acetyltransferase 10 (NAT10), a protein with high biological relevance for aging and cancer. We performed a comprehensive survey of ac⁴C using metabolic labeling, sodium cyanoborohydride chemical treatment coupled to next-generation sequencing (NGS), and ac⁴C antibody-based cell and molecular biology techniques. Our analysis shows that NAT10-dependent ac⁴C-acetylation is robust in rRNA and specific tRNAs but low/spurious in mRNA. It also...
Turja K Debnath

TRIM15 drives chondrocyte senescence and osteoarthritis progression

1 year ago
Osteoarthritis (OA) is a prevalent joint disease characterized by pain, disability, and loss of physical function, posing a challenge to public health. However, molecular mechanisms of OA pathogenesis have not been fully described. We report that tripartite motif containing 15 (TRIM15) is a regulator in chondrocyte senescence and OA. Our study revealed heightened expression of TRIM15 in chondrocytes of senescent cartilage from patients with OA and in aged wild-type mice. Using gain- and...
Zhuang Li

Overexpression of betaTrCP1 elicits cell death in cisplatin-induced senescent cells

1 year ago
Senescence is a non-proliferative cellular state derived from aging or in response to exogenous insults, such as those that cause DNA damage. As a result of cancer treatments like cisplatin, certain tumor cells may undergo senescence. However, rather than being beneficial for patients, this is detrimental because these cells might proliferate again under specific conditions and, more importantly, because they synthesize and secrete molecules that promote the proliferation of nearby cells....
Alejandro Belmonte-Fernández

FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1

1 year ago
Aging is characterized by changes in gene expression, some of which can drive deleterious cellular phenotypes and senescence. The transcriptional activation of senescence genes has been mainly attributed to epigenetic shifts, but the changes in chromatin accessibility and its underlying mechanisms remain largely elusive in natural aging. Here, we profiled chromatin accessibility in human dermal fibroblasts (HDFs) from individuals with ages ranging from neonatal to octogenarian. We found that...
Fábio J Ferreira

Atomic-scale self-rearrangement of hetero-metastable phases into high-density single-atom catalysts for the oxygen evolution reaction

1 year ago
Maximizing metal-substrate interactions by self-reconstruction of coadjutant metastable phases can be a delicate strategy to obtain robust and efficient high-density single-atom catalysts. Here, we prepare high-density iridium atoms embedded ultrathin CoCeOOH nanosheets (CoCe-O-Ir(SA)) by the electrochemistry-initiated synchronous evolution between metastable iridium intermediates and symmetry-breaking CoCe(OH)(2) substrates. The CoCe-O-Ir(SA) delivers an overpotential of 187 mV at 100 mA...
Quan Quan

Activating fast and reversible sodium storage in NASICON cationic defect sites through fluorine doping

1 year ago
Cycling positive electrode materials with high voltages and long lifetimes remains a challenge. On the one hand, operating electrodes at high voltages is usually accompanied by severe structural distortions and irreversible reactions. On the other hand, the significant volume variation upon Na^(+) insertion/extraction limits the long cycling life. Here, we report a defective positive electrode material with a chemical formula of Na(3.2)□(0.8)Co(0.5)Fe(0.5)V(PO(3.9)F(0.1))(3) (□ represents Na...
Jingrong Hou

Prognostic impact of a senescence gene signature in multiple myeloma

1 year ago
Multiple myeloma (MM), an incurable malignancy of plasma cells, is predominantly an age-related disease, with the majority of cases occurring in patients over the age of 60. Cellular senescence, a fundamental biological process underlying aging, has been increasingly recognized for its critical role in developing age-related malignancies. In this study, we aimed to investigate the prognostic significance of genes implicated in the molecular mechanisms of senescence within a large cohort of MM...
Andrea Lehoczki

Prediction of population aging trend and analysis of influencing factors based on grey fractional-order and grey relational models: a case study of Jiangsu Province, China

1 year ago
CONCLUSIONS: In conjunction with the analysis results from FGM(1,1) model and GRA of panel data, this study enhances the comprehensive understanding of the aging issue in Jiangsu Province. The insights derived herein offer crucial data support and a scientific foundation for both Jiangsu Province and the Chinese government to develop policies addressing population aging. Considering the anticipated future trends in aging, it is recommended that the government revise fertility policies to...
Xiaojun Guo

Examining the Heterogeneity of Exercise Response Among Sedentary Older Adults: A Descriptive Analysis

1 year ago
Background: Significant heterogeneity in individual responses to exercise interventions provides an opportunity to identify individuals for whom modifications or adjunct therapies may be necessary. Here, we explore heterogeneity of exercise response among people with HIV (PWH) versus without HIV (control). Methods: The Exercise for Healthy Aging Study enrolled sedentary older PWH and controls (50-75 years old) for a 24-week aerobic and resistance exercise program. Responder groups were...
Grace L Kulik
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