TY  - JOUR
A1  - Klaus, Susanne
A1  - Ost, Mario
T1  - Mitochondrial uncoupling and longevity
BT  - a role for mitokines?
JF  - Experimental gerontology
N2  - Aging has been viewed both as a random process due to accumulation of molecular and cellular damage over time and as a programmed process linked to cellular pathway important for growth and maturation. These views converge on mitochondria as both the major producer of damaging reactive oxidant species (ROS) and as signaling organelles. A finite proton leak across the inner mitochondrial membrane leading to a slight uncoupling of oxidative phosphorylation and respiration is an intrinsic property of all mitochondria and according to the "uncoupling to survive" hypothesis it has evolved to protect against ROS production to minimize oxidative damage. This hypothesis is supported by evidence linking an increased endogenous, uncoupling protein (UCP1) mediated, as well as experimentally induced mitochondrial uncoupling to an increased lifespan in rodents. This is possibly due to the synergistic activation of molecular pathways linked to life extending effects of caloric restriction as well as a mitohormetic response. Mitohormesis is an adaptive stress response through mitonuclear signaling which increases stress resistance resulting in health promoting effects. Part of this response is the induction of fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), two stress-induced mitokines which elicit beneficial systemic metabolic effects via endocrine action.
KW  - Uncoupling proteins
KW  - Energy metabolism
KW  - Skeletal muscle
KW  - Mitohormesis
KW  - GDF15
KW  - FGF21
Y1  - 2019
U6  - https://doi.org/10.1016/j.exger.2019.110796
SN  - 0531-5565
SN  - 1873-6815
VL  - 130
PB  - Elsevier Science
CY  - Amsterdam
ER  -