Science of Aging

Calorie restriction reduces oxidative stress by Boosting Primary Antioxidant Defense

It has been almost years , Bob Cavanaugh is practicing severe calorie restriction. Bob Cavanaugh, managing director of the Calorie Restriction Society, is among the first to practice calorie restriction. Although the effect of “calorie restriction “ on humans is yet unknown, some are undertaking this bid to live longer . For years there has been evidence that diet low in calories extends life span. Yet we do not completely understand molecular mechanism involved in Life span extension by calorie restriction. One theory is that state of hunger act as mild stressor that makes an organism resistant to ill effect of aging. 

So how do calorie restriction evoke an anti stress response? In a recent publication in cell metabolism, a group of Berkeley Lab researchers have shown that Calorie restriction reduces oxidative stress by activating superoxide dismutase an antioxidant enzyme. Free radicals are highly reactive chemical entities that are produced as byproduct of normal metabolic process. The antioxidant defense system consisting of enzymes including superoxide dismutase protects cells from free radical assault. A major cause of aging and numerous diseases is thought to be cumulative oxidative stress, resulting from the production of reactive free radicals during respiration.

In this study the researchers created a knockout mice missing a gene that produces a mitochondrial enzyme Sirt3. Under similar calorie restriction regime, the Knockout mouse failed to respond to beneficial effects of CR such as reduction in oxidative stress. Further it was shown that sirt3 reduces cellular free radicals by activating a crucial antioxidant enzyme superoxide dismutase. It removes acetyl moiety from two critical lysine residues on SOD and promotes its free radical scavenging activity.  

The study takes us one step closer to understanding the molecular mechanism involved in life span extension by CR. 

Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab: 12(6):662-667.