Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 44

Several quality control mechanisms maintain intracellular protein homeostasis, or proteostasis: misfolded proteins can be refolded by chaperone proteins or degraded by the ubiquitin‐proteasome system and lysosomal pathways (the latter phenomenon being referring as autophagy). An increase in protein misfolding (due to cellular stress, for instance) and/or failure of quality control mechanisms is thought to contribute to ageing and age‐related diseases, typically Alzheimer’s and cataracts.^37,38 Mice deficient in the CHIP co‐chaperone exhibit accelerated‐ageing phenotypes and reduced lifespan,³⁹ and mice overexpressing Atg5 (a protein essential for autophagosome formation) have better motor function and increased lifespan. In humans, autophagy appears to be better maintained in offspring of individuals with exceptional longevity and is associated with higher effector functions of T lymphocytes. Interestingly, the lifespan‐extending effect of drugs (e.g. rapamycin) shown in mice may be mediated by their autophagy‐inducing properties.⁴⁰ Thus, loss of mechanisms controlling protein homeostasis, especially autophagy, may be involved in ageing, and there is growing interest in measuring these mechanisms as markers of biological age.²⁷