Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease

Jan      Suski; Magdalena      Lebiedzinska; Nuno      G. Machado; Paulo      J. Oliveira; Paolo      Pinton; Jerzy      Duszynski; Mariusz      R. Wieckowski

Abstract

Better understanding of the effect of ageing on mitochondrial metabolism and of the mechanisms of action of various drugs is required to allow optimization of the treatment of many diseases with minimized risk of dangerous impairment of mitochondrial function. Numerous reports show that efficacy of medical treatment depends on the age of treated subjects. This applies particularly to the effect of drugs on various senescence-prone cellular pathways. In this review, we demonstrate how ageing affects various mitochondria-associated pathways and their response to a variety of factors. These factors include registered drugs and other chemicals, and account for diverse consequences which vary depending on the physiological condition. Pharmacological treatments aimed at improving mitochondrial function should thus have in mind the subject age.

Keywords: Mitochondria, ageing, drugs, toxic agents, respiratory chain, oxidative phosphorylation, oxidative stress, ROS, hispidin, antiretroviral therapy