From discoveries in ageing research to therapeutics for healthy ageing

Nature, Journal Year: 2019, Volume and Issue: 571(7764), P. 183 - 192

Published: July 10, 2019

Language: Английский

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Autophagy in healthy aging and disease

Nature Aging, Journal Year: 2021, Volume and Issue: 1(8), P. 634 - 650

Published: Aug. 12, 2021

Language: Английский

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DNA methylation aging clocks: challenges and recommendations

Genome biology, Journal Year: 2019, Volume and Issue: 20(1)

Published: Nov. 25, 2019

Abstract Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These are acknowledged as highly accurate molecular correlate chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates test longevity or rejuvenating interventions. Here, we discuss key challenges understand clock mechanisms biomarker utility. This requires dissecting the drivers regulators age-related changes single-cell, tissue- disease-specific models, well exploring epigenomic marks, longitudinal diverse population studies, non-human models. We also highlight important ethical issues forensic determination predicting trajectory an individual.

Language: Английский

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ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease

Antioxidants, Journal Year: 2020, Volume and Issue: 9(8), P. 743 - 743

Published: Aug. 13, 2020

Neurodegenerative disorders, such as Alzheimer’s disease, are a global public health burden with poorly understood aetiology. Neuroinflammation and oxidative stress (OS) undoubtedly hallmarks of neurodegeneration, contributing to disease progression. Protein aggregation neuronal damage result in the activation disease-associated microglia (DAM) via damage-associated molecular patterns (DAMPs). DAM facilitate persistent inflammation reactive oxygen species (ROS) generation. However, mechanisms linking OS have not been well-defined; thus targeting these cells for clinical benefit has possible. In microglia, ROS generated primarily by NADPH oxidase 2 (NOX2) NOX2 is associated DAMP signalling, amyloid plaque deposition, especially cerebrovasculature. Additionally, originating from both NOX mitochondria may act second messengers propagate immune activation; intracellular signalling underlie excessive OS. Targeting key kinases inflammatory response could cease promote tissue repair. Expression antioxidant proteins dehydrogenase 1 (NQO1), promoted transcription factor Nrf2, which functions control limit Lipid droplet accumulating (LDAM) also represent double-edged sword neurodegenerative sequestering peroxidised lipids non-pathological ageing but becoming dysregulated pro-inflammatory disease. We suggest that future studies should focus on targeted manipulation understand driving inflammatory-related activation. Finally, we discuss recent evidence therapeutic target identification be unbiased founded relevant pathophysiological assays discovery translatable anti-inflammatory therapeutics.

Language: Английский

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Physical activity and exercise: Strategies to manage frailty

Redox Biology, Journal Year: 2020, Volume and Issue: 35, P. 101513 - 101513

Published: March 20, 2020

Frailty, a consequence of the interaction aging process and certain chronic diseases, compromises functional outcomes in elderly substantially increases their risk for developing disabilities other adverse outcomes. Frailty follows from combination several impaired physiological mechanisms affecting multiple organs systems. And, though frailty sarcopenia are related, they two different conditions. Thus, strategies to preserve or improve status should consider systemic function addition muscle conditioning. Physical activity/exercise is considered one main counteract frailty-related physical impairment elderly. Exercise reduces age-related oxidative damage inflammation, autophagy, improves mitochondrial function, myokine profile, insulin-like growth factor-1 (IGF-1) signaling pathway, insulin sensitivity. interventions target resistance (strength power), aerobic, balance, flexibility work. Each type aspects functioning, could be combined according need prescribed as multicomponent intervention. Therefore, exercise intervention programs based on an individual's functioning adapted ensuing response.

Language: Английский

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The quest to slow ageing through drug discovery

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(8), P. 513 - 532

Published: May 28, 2020

Language: Английский

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The probabilistic model of Alzheimer disease: the amyloid hypothesis revised

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(1), P. 53 - 66

Published: Nov. 23, 2021

Language: Английский

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Measuring biological age using omics data

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 715 - 727

Published: June 17, 2022

Language: Английский

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A meta-analysis of genome-wide association studies identifies multiple longevity genes

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 14, 2019

Abstract Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA a rigorous phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to 90th/99th survival percentile, respectively, and 25,483 controls whose death last contact was below 60th percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) associated lower odds 90th 99th percentile age, while rs7412 (ApoE ε2) shows opposite. Moreover, rs7676745, located near GPR78 , associates age. Gene-level analysis reveals role for tissue-specific expression multiple genes in longevity. Finally, genetic correlation results that several disease-related phenotypes points shared architecture between health

Language: Английский

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The genetics of human ageing

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 21(2), P. 88 - 101

Published: Nov. 5, 2019

Language: Английский

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