Mitochondrial heat shock protein 70 (mthsp70) functions as a mitochondrial import motor and is essential in mitochondrial biogenesis and energy generation in eukaryotic cells. HSP-6 (hsp70F) is a nematode orthologue of mthsp70. Knockdown of HSP-6 by RNA interference in young adult nematodes caused a reduction in the levels of ATP-2, HSP-60 and CLK-1, leading to abnormal mitochondrial morphology and lower ATP levels. As a result, RNA interference-treated worms had lower motility, defects in oogenesis, earlier accumulation of autofluorescent material, and a shorter life span. These are the major phenotypes observed during the aging of worms, suggesting that the reduction of HSP-6 causes early aging or progeria-like phenotypes. The amount of HSP-6 became dramatically reduced at the expected mean life span in not only wild-type but also in long and short life span mutant worms (wild-type, daf-2, and daf-16). Mitochondrial HSP-60 and ATP-2 were also reduced following the reduction of HSP-6 during aging. These results suggest that the reduction of HSP-6 causes defects in mitochondrial function at the final stage of aging, leading to mortality.Mitochondria are major organelles that carry out cellular oxidation and produce most of the cellular ATP by oxidative phosphorylation. Mitochondria also play essential roles in controlling cell viability and proliferation (1, 2). A large number of studies have shown the essential roles of mitochondria in development and differentiation (3, 4). Furthermore, mitochondria are thought to be deeply involved in the aging process, based on the free radical theory of aging, because mitochondria are a major source of reactive oxygen species (ROS) 3 (5, 6). Accumulating evidence supports this idea. For example, abnormal mitochondria accumulate during aging (7), and enforced breakdown of mtDNA or their repair mechanism causes premature aging in mice (8,9). In Caenorhabditis elegans, mutations in mev-1 (a subunit of the enzyme succinate dehydrogenase cytochrome b, a component of complex II of the mitochondrial electron transport chain) and gas-1 (a subunit of mitochondrial NADH-ubiquinone oxidoreductase, a component of complex I of the mitochondrial electron transport chain) increase ROS production and sensitivity to stress, resulting in a shorter life span (10 -13).A mammalian mitochondrial heat shock protein 70 (mthsp70, also known as mortalin or Grp75) has been shown to function as a mitochondrial protein import motor and is involved in mitochondrial biogenesis (14, 15). It has also been shown to be involved in the production of ROS (16), cell proliferation (17), and the regulation of life span (18) in mammalian cells. Increased expression of HSP-6 (hsp70F), the predicted C. elegans orthologue of mthsp70, by the introduction of an extra hsp-6 gene copies extended the life span of C. elegans (19). In contrast, deletion mutations of SSC1, the yeast orthologue of mthsp70, were lethal (20 -22), and knockdown of mthsp70 caused growth arrest in human cancer cells (17,23). Recently, it has been ...