Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress.

Heat shock proteins (Hsp) are involved in protein folding, transport and stress resistance. Studies reporting an increased mRNA level of hsp genes in aged Drosophila suggest that expression of Hsp might be beneficial in preventing damages induced by aging. Because oxidative damage is often observed in aged organisms and mitochondria are sensitive to reactive oxygen species, we tested the hypothesis that increased levels of a small Hsp localized in mitochondria, Hsp22 of Drosophila melanogaster, could protect mitochondrial proteins and influence the aging process. We demonstrate that a ubiquitous or a targeted expression of Hsp22 within motorneurons increases the mean life span by more than 30%. Hsp22 shows beneficial effects on early-aging events since the premortality phase displays the same increase as the mean lifespan. Moreover, flies expressing Hsp22 in their motorneurons maintain their locomotor activity longer as assessed by a negative geotaxis assay. The motorneurons-targeted expression of Hsp22 also significantly increases flies' resistance to oxidative injuries induced by paraquat (up to 35%) and thermal stress (39% at 30 degrees C and 23% at 37 degrees C). These observations establish Hsp22 as a key player in cell-protection mechanisms against oxidative injuries and aging in Drosophila and corroborate the pivotal role of mitochondria in the process of aging.