AGING AS A CONSEQUENCE OF MISREPAIR -- A NOVEL THEORY OF AGING

Jicun Wang (1) , Thomas Michelitsch (2) , Arne Wunderlin (3) , Ravi Mahadeva (1)

1 CUH - Department of Medicine, Addenbrooke's Hospital, University of Cambridge
2 DALEMBERT - Institut Jean Le Rond d'Alembert
3 Universität Stuttgart [Stuttgart]

It is now increasingly realized that the underlying mechanism which governs aging (ageing) is a complex interplay of genetic regulation and damage-accumulation. "Aging as a result of accumulation of 'faults' on cellular and molecular levels", has been proposed in the damage (fault)-accumulation theory. However, this theory fails to explain some aging phenotypes such as fibrosis and premature aging, since terms such as 'damage' and 'fault' are not specified. Therefore we introduce some crucial modifications of this theory and arrive at a novel theory: aging of the body is the result of accumulation of Misrepair of tissue. It emphasizes: a) it is Misrepair, not the original damage, that accumulates and leads to aging; and b) aging can occur at different levels, however aging of the body takes place necessarily on the tissue level, but not requiring the aging of cells/molecules. The Misrepair-accumulation theory introduced in the present paper unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. This theory gives explanations for the aging phenotypes, premature aging, the difference of longevity in different species, and it is consistent with the physical view on complex systems.

Mots clés: aging (ageing); damage; Misrepair-accumulation; longevity; complex adaptive systems

Domaines: Autre [q-bio.OT]; Biologie du développement

Jicun Wang, Thomas Michelitsch, Arne Wunderlin, Ravi Mahadeva. AGING AS A CONSEQUENCE OF MISREPAIR -- A NOVEL THEORY OF AGING. 2011. ⟨hal-00373085v3⟩