UCP1 Extends Longevity Via Hormesis?

Uncoupling proteins affect mitochondrial function, altering the balance of energy going to heat versus building ATP molecules to store it for use elsewhere. Like a range of other mitochondrial manipulations, altering levels of uncoupling proteins can extend life in laboratory animals, and here researchers suggest this works via hormesis, causing just enough damage to spur repair mechanisms to greater ongoing effects for a net overall gain:

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria considerably increases lifespan in high fat diet fed UCP1 transgenic (TG) mice in comparison to wildtype (WT).

In order to clarify the underlying mechanisms we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low fat and high fat fed mice. TG mice [showed] elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress protective heat shock protein 25.

We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. All together our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23277187

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