Bioenergetics and Mitochondrial Dysfunction in Aging: Recent Insights for a Therapeutical Approach

Abstract

The present review points out the role of oxidative stress in aging and the potential therapeutic targets of modern antioxidant therapies. Mitochondria are essential for several biological processes including energy production by generating ATP through the electron transport chain (ETC) located on the inner mitochondrial membrane. Due to their relevance in cellular physiology, defects in mitochondria are associated with various human diseases. Moreover, several years of research have demonstrated that mitochondria have a pivotal role in aging. The oxidative stress theory of aging suggests that mitochondria play a key role in aging as they are the main cellular source of reactive oxygen species (ROS), which indiscriminately damage macromolecules leading to an age-dependent decline in biological function. In this review we will discuss the mitochondrial dysfunction occurring in aging. In particular, we will focus on the novel mitochondria targeted therapies and the new selective molecules and nanocarriers technology as potentially effective in targeting mitochondrial dysfunction and diseases involving oxidative stress and metabolic failure.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications

“…Mitochondrial dysfunction is a feature of normal aging and age‐related diseases, including obesity, type 2 diabetes, and metabolic syndrome (35). It is also essential for normal tissue metabolism, and mitochondrial dysfunction has been shown to alter adipocyte differentiation and function (8, 10, 11).…”

Cytochrome P450-2E1 promotes aging-related hepatic steatosis, apoptosis and fibrosis through increased nitroxidative stress

“…8D). This is not surprising since most of hepatic ATP production have been reported to remain unchanged during the aging process, possibly through an adaptive mechanism [67], although decreased ATP production during aging process was also documented [68]. The potential role of mitochondria in mediating the hepatic aging-related changes in WT mice needs additional investigation to further establish their importance in the aging process.…”

Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders

“…Mitochondria play a central role in ROS generation, a process closely associated with ATP production (Boveris and Cadenas, 1975;Cadenas and Davies, 2000;Han et al, 2001;Romano et al, 2014).Oxygen captures electrons "leaking" from the electron transport chain forming superoxide, which permutates into hydrogen peroxide and molecular oxygen in a reaction catalyzed by mitochondrial superoxide dismutase. Notably, this reaction is both spontaneous and fast, with rate constants for the noncatalyzed and superoxide dismutase 2-catalyzed reactions of 5 × 10 5 mol −1 sec −1 and 1.6 × 10 9 mol −1 sec −1 , respectively.…”