Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster

Rana A, Oliveira MP, Khamoui AV, Aparicio R, Rera M, Rossiter HB, Walker DW

https://www.nature.com/articles/s41467-017-00525-4 

• Transient induction of Drp1-mediated fission for 7 days during midlife of the fruit fly D. melanogaster is sufficient to extend lifespan. (Note that Drp-1 upregulation in early life had no significant impact on longevity)
• Short-term midlife Drp1 induction gave increased day-time physical activity levels, suggesting an extension of healthy lifespan, rather than prolonging frailty. These flies also had improved starvation resistance, improved fertility, and delayed intestinal aging.
• In flight muscle, elongated mitochondrial morphology was associated with lowered mitochondrial membrane potential, accumulation of dysfunctional mitochondria, lowered OXPHOS complex activity, increased ROS and lowered respiration with aging. These phenotypes are reversed upon short-term midlife Drp1 induction.
• These effects were not mediated by the mitochondrial unfolded protein response. 
• Short-term midlife Drp1 induction reduced levels of protein aggregates in aged muscle and aged brain tissue
• Disruption of mitophagy, via Atg1 inhibition, inhibits the anti-aging effects of midlife Drp1 induction.