Aged mice given modified TFAM showed improvements in memory and exercise performance compared with untreated mice. "It was like an 80-year-old recovering the function of a 30-year-old," says Rafal Smigrodzki, also at Gencia, who presented the results at the Strategies for Engineered Negligible Senescence conference in Cambridge this month.
Targeted mitochondrial therapeutics in aging (SENS 6)
Mitochondrial dysfunction in aging consists of relative suppression of oxidative phosphorylation and frequently an increase in glycolysis. This metabolic imbalance is triggered by progressive biochemical processes, including accumulation of mitochondrial mutations, and changes in the expression and function of nuclear-encoded mitochondrial proteins. Our group developed methods for mitigation of mitochondrial suppression through mitochondria-targeted therapeutics. We observed that stimulation of mitochondrial activity both in vitro and in vivo significantly improves cellular function, suppresses neoplastic growth and inflammation, improves aged animal cognition and resolves in vivo metabolic derangements. One of our therapeutics, an engineered mitochondrial transcription factor, prolonged survival in wild-type aged animals. We expect that mitochondrial stimulation will be an important part of future aging therapies.
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