| Abstract: | A progressive dysfunction of the mitochondrion probably plays a decisive role in the aging process. In the present hypothesis it is suggested that the functional defect specifically concerns the catalytic subunit of the mitochondrial F1-ATPase.This proposal is based on observations concerning two classical models of the aging process. - 1. 1. The Werner syndrome of premature aging is autosomally recessive; meaning that this disorder — in analogy with other recessive inborn errors of metabolism — results from a single specific mutation, typically resulting in an enzyme defect.
- 2. 2. The strong association between the ATPase activity of the SV40 T-antigen and the process of cellular immortalization in vitro, suggests that the putative enzyme dysfunction could concern an ATPase.
The decrease with aging in the activity of the mitochondrial F1-ATPase — the main producer of ATP — could lay behind the progressive lack of homeostasis observed in senescence. |
