Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function

https://www.nature.com/articles/s41419-018-0765-9

Bhupendra Singh, Trenton R. Schoeb, Prachi Bajpai, Andrzej Slominski & Keshav K. Singh

• The authors created an inducible mouse expressing a dominant negative mutant of POLG1 which induces mtDNA depletion (approximately x2 depletion) in the whole animal (mtDNA-depleter mouse). 
• The depletion of mtDNA caused widespread reduction in activity of components of the electron transport chain.
• Skin wrinkles and hair loss were amongst the earliest and most predominant phenotypic changes, along with a reduction in body weight and height, and skin inflammation
• The authors induced mtDNA depletion for 2 months, resulting in the above phenotypes, then restored mtDNA copy number. After 1 month at normal mtDNA copy number, skin wrinkles and hair loss reverted, and the animals displayed relatively normal cutaneous structures. Skin inflammation reduced, although was not returned fully to wild-type levels. 
• This study is further evidence for the causal role of mtDNA perturbations in mammalian ageing, and is amongst the first studies to demonstrate that mtDNA-induced ageing may be reversible.