Shortened life span premature aging

One of the most provocative uses of a manganese-containing compound is extending the lifespan. A SOD mimetic, manganese 5,10,15,20-tetrakis-(4-benzoic acid) porphyrin (MnTBAP) (Figure 9.4), was administered by intraperitoneal injection to mice with a SOD2 knockout. Use of this synthetic antioxidant in these transgenic mice increased the survival time by 100%, from 8 to 16 days of age.13 Cardiac pathology and lipid accrual in the liver were reduced but the mice developed neurological disorders at day 12, due to a spongiform encephalopathy. Since the MnTBAP was unable to cross the

COOH

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Figure 9.4 SOD mimetic Mn(III) 5,10,15,20-tetrakis-(4-benzoic acid) porphyrin (MnTBAP)

blood-brain barrier, the ultrastructural changes in the brain were attributed to age-related oxidative damage that was allowed to proceed with the alleviation of the cardiomyopathy.

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