Mitochondrial peptidase XXXX mutation causes early onset of age-associated disorders and impairs adult stem cell self-renewal.

@entity66817 @entity17864 @entity19 @entity75 @entity26 @entity1513 @entity6288 @entity224 @entity2055
Mitochondrial reactive @entity26 species (ROS) are proposed to play a central role in aging and age-associated disorders, although direct in vivo evidence is lacking. We recently generated a @entity19 mutant with mutated @entity66817 ( @entity66817 ) gene, which impairs the signal peptide sequence processing of mitochondrial proteins cytochrome c1 and @entity17864 dehydrogenase 2. The mitochondria from mutant @entity19 generate elevated levels of @entity224 ion and cause impaired fertility in both sexes. Here, we design experiments to examine the effects of excessive mitochondrial ROS generation on health span. We show that @entity66817 mutation increases oxidative stress in multiple organs such as the brain and the kidney, although expression of @entity224 dismutases in these tissues of the mutants is also increased. The mutants show multiple aging-associated phenotypes, including wasting, @entity6288 , loss of subcutaneous fat, @entity1513 , and @entity2055 , with female mutants showing earlier onset and more severe age-associated disorders than male mutants. The loss of body weight and fat was unrelated to food intake. Adipose-derived stromal cells (ADSC) from mutant @entity19 showed impaired proliferation capability, formed significantly less and smaller colonies in colony formation assays, although they retained adipogenic differentiation capability in vitro. This functional impairment was accompanied by increased levels of oxidative stress. Our data showed that mitochondrial ROS is the driving force of accelerated aging and suggested that @entity75 to adult stem cells could be one of the mechanisms for age-associated disorders.
