Cellular senescence at the crossroads of inflammation and Alzheimer's disease.

Trends Neurosci

UK Dementia Research Institute, Institute of Neurology, University College London, London WC1E 6BT, UK; The Francis Crick Institute, London NW1 1AT, UK. Electronic address:

Published: September 2021

Aging is a key risk factor for Alzheimer's disease (AD), but the reasons for this association are not well understood. Senescent cells accumulate in aged tissues and have been shown to play causal roles in age-related pathologies through their proinflammatory secretome. The question arises whether senescence-induced inflammation might contribute to AD and bridge the gap between aging and AD. Here, we highlight the role of cellular senescence as a driver of the aging phenotype, and discuss the current evidence that connects senescence with AD and neurodegeneration.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tins.2021.06.007DOI Listing

Publication Analysis

Top Keywords

cellular senescence
8
alzheimer's disease
8
senescence crossroads
4
crossroads inflammation
4
inflammation alzheimer's
4
disease aging
4
aging key
4
key risk
4
risk factor
4
factor alzheimer's
4

Similar Publications

N4-acetylcytidine (ac4C) modification is a crucial RNA modification widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays a pivotal role in viral infections. Despite numerous studies highlighting the strong correlation between ac4C modification and cancer progression, its detailed roles and molecular mechanisms in normal physiological processes and cancer progression remain incompletely understood.

View Article and Find Full Text PDF

Contemporary therapies following heart failure center on regenerative approaches to account for the loss of cardiomyocytes and limited regenerative capacity of the adult heart. While the delivery of cardiac progenitor cells has been shown to improve cardiac function and repair following injury, recent evidence has suggested that their paracrine effects (or secretome) provides a significant contribution towards modulating regeneration, rather than the progenitor cells intrinsically. The direct delivery of secretory biomolecules, however, remains a challenge due to their lack of stability and tissue retention, limiting their prolonged therapeutic efficacy.

View Article and Find Full Text PDF

Maximizing the life-long reproductive output would lead to the prediction that short-lived and fast aging species would undergo no - if any - reproductive senescence. Turquoise killifish (Nothobranchius furzeri) are naturally short-lived teleosts, and undergo extensive somatic aging, characterized by molecular, cellular, and organ dysfunction following the onset of sexual maturation. Here, we tested whether naturally short-lived and fast aging male turquoise killifish maximize reproduction and display minimal - if any, reproductive senescence.

View Article and Find Full Text PDF

Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.

View Article and Find Full Text PDF

Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors.

J Immunother Cancer

January 2025

Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People's Republic of China

Background: Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors.

Methods: In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto the adoptive T cell surface via bioorthogonal reactions, aiming to specifically inhibit the group IVA cytosolic phospholipase Aα (cPLAα), a key enzyme facilitating phospholipid metabolism and senescent state of T cells.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!