Fat Tissue Knockout of Mitochondrial Transcription Factor A is Beneficial, and May Extend Life in Mice

Mitochondrial transcription factor A (TFAM) plays a number of important roles and shows up in connection with protofection research aimed at mitochondrial repair. Separately, researchers observe benefits by removing it from the fat tissue of mice:

Mutations in genes involved in the electron transport chain that cause mitochondrial dysfunction can sometimes paradoxically lead to improved health and/or enhanced longevity. One example is the situation in mice with conditional knockout of the mitochondrial transcription factor A (TFAM) specifically in fat. These F-TFKO mice exhibit mitochondrial dysfunction with increased energy expenditure, but are protected from age- and diet-induced obesity, insulin resistance and hepatosteatosis, despite increased food intake.

Mitochondrial DNA (mtDNA) is maternally inherited with multiple copies in each mitochondria. TFAM plays a critical role in maintenance and expression of mtDNA, and reductions of mtDNA copy number usually correlate with reduction of mitochondria content and function. So, how does a reduction in TFAM in fat have this beneficial effect?

Upon high fat diet, [the F-TFKO] mice develop a build-up of long chain acyl carnitines in both adipose tissue and the circulation. In addition, markers of oxidative stress are observed at the level of DNA and lipids in adipose tissue of F-TFKO mice on high fat diet, indicating overload of the ROS protection system. Despite this mitochondria stress, the mice remain lean and insulin sensitive even at 10 months of age. Although no formal aging studies have been conducted in these mice, we also noted that by 18 months of age, an age at which the control mice have started to die, the F-TFKO mice are still thriving, suggesting this knockout may be beneficial to aging mice as well.

Link: http://impactaging.com/papers/v4/n12/full/100518.html

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