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 mechanisms which govern aging (ageing) are 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 by Kirkwood 2006. 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 here a specification of the underlying mechanism of aging and arrive at a novel theory: aging of the body is a result of the 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 at least on the tissue level, but not necessarily on cellular/molecular level. The novel concept of Misrepair introduced here unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. The Misrepair-accumulation theory introduced in the present paper gives explanations for the aging phenotypes, premature aging, and the difference of longevity in different species, and is consistent with the point of view of physical theory of complex adaptive 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. 2009. ⟨hal-00373085v2⟩