A physicochemical perspective on cellular ageing

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) 2023-11, Vol.48 (11), p.949-962
• Main Authors: Mouton, Sara N., Boersma, Arnold J., Veenhoff, Liesbeth M.
• Format: Article
• Language: English
• Subjects: cell volume; Cellular Senescence; macromolecular crowding; organellar crowding; Oxidation-Reduction; redox homeostasis; yeast
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2023.08.007

Ageing is a complex, multifactorial process which cannot be fully explained by molecular mechanisms.The physicochemical intracellular environment provides a backdrop to all molecular mechanisms.Yeast replicative ageing is associated with changes in multiple physicochemical parameters, including the pH of the cytosol, vacuole, and cell cortex, as well as redox state and organellar crowding.Changes in physicochemical parameters impinge on aspects of the molecularly defined hallmarks of ageing, including loss of protein homeostasis, genome instability, and mitochondrial function.A change in physicochemical parameters during ageing is an aspect that emerges as a potential contributor, or even driver, of age-related diseases. Cellular ageing described at the molecular level is a multifactorial process that leads to a spectrum of ageing trajectories. There has been recent discussion about whether a decline in physicochemical homeostasis causes aberrant phase transitions, which are a driver of ageing. Indeed, the function of all biological macromolecules, regardless of their participation in biomolecular condensates, depends on parameters such as pH, crowding, and redox state. We expand on the physicochemical homeostasis hypothesis and summarise recent evidence that the intracellular milieu influences molecular processes involved in ageing. Cellular ageing described at the molecular level is a multifactorial process that leads to a spectrum of ageing trajectories. There has been recent discussion about whether a decline in physicochemical homeostasis causes aberrant phase transitions, which are a driver of ageing. Indeed, the function of all biological macromolecules, regardless of their participation in biomolecular condensates, depends on parameters such as pH, crowding, and redox state. We expand on the physicochemical homeostasis hypothesis and summarise recent evidence that the intracellular milieu influences molecular processes involved in ageing.