Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 43

According to the historical mitochondrial free radical ‘theory’ of ageing,³⁴ progressive mitochondrial dysfunction reduces energy availability and increases the production of reactive oxygen species (ROS) that damage macromolecules, contributing to ageing. Nevertheless, this theory has been reshaped in light of observations that (i) increased ROS may prolong lifespan in model organisms, (ii) increased ROS production and oxidative damage do not accelerate ageing in mice, and (iii) experimental mitochondrial dysfunction may accelerate ageing without ROS production.³⁵ Therefore, ROS may be considered a stress‐induced survival signal response to ageing‐related damage, which will eventually aggravate the process if antioxidant systems are overwhelmed. ROS‐independent mechanisms of mitochondrial dysfunction include a propensity to stress‐induced permeabilisation, reduced mitochondria biogenesis, and reduced quality control by autophagy (see the following section).¹⁵

Interestingly, mitochondrial metabolic function can now be measured in vivo, and it has been shown to be associated with muscle strength and mobility in older people.³⁶ Measures of mitochondrial physiology and function may thus be powerful markers of biological ageing but need careful standardisation.²⁷