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Scientists discover molecular 'switch' that contributes to cellular aging process
Date:11/30/2010

ative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on.

The scientists knew that oxidative damage causes the body to age. What they did not know is why aged cells have more oxidative damage. "The significance of our study is that we show SMRT facilitates this process," Lee said. "In other words, the normal metabolic homeostasis is maintained, in part, by PPARs. SMRT acts as a metabolic switch to turn off PPAR activities when the cells age."

PPAR drugs have been used to increase insulin sensitivity and lower blood lipid levels. "Our study shows PPARs might also be used to boost the body's ability to handle oxidative stress," Lee said.

"With what we have learned, we believe SMRT is one of the key players that causes age-dependent decline in mitochondrial function by blocking PPAR activity, and we've found a way to boost the body's ability to better handle metabolic and oxidative stress," Lee said. "This finding is significant since increased oxidative stress, coupled with reduced metabolic function, contributes to the aging process and the development of age-related metabolic diseases."

In collaboration with epidemiologists at HSPH, the team found genetic variations in the human SMRT gene that are associated with risk of type 2 diabetes. "Through this study we were able to validate that our findings in the animal model apply to human diseases," Lee said.


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Contact: Marjorie Dwyer
mhdwyer@hsph.harvard.edu
617-384-8995
Harvard School of Public Health
Source:Eurekalert

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