Miroslav Radman
Radman, Miroslav
Mediterranean Institute for Researching Life
Split, Croatia
Title: Molecular Basis of Biological Robustness
Authors: Miroslav Radman
Abstract:To learn how could oraganisms better resist macromolecular damages that cause aging and cancer, we have studied highly robust organisms, e.g., bacterium Deinococcus radiodurans and the aquatic animals Bdelliod Rotifers (collaboration with Prof. M. Meselson, Harvard University), both extremely resistant to desiccation and radiations. So far we have learned the following:

(1) DNA is equally susceptible to double-strand breakage (DSB) in robust and sensitive species. What matters for survival is the efficacy of DNA repair systems [1]. (2) D. radiodurans did not acquire any recognizable new DNA repair activities [2], instead: (3) Both D. radiodurans and the rotifer Adineta vaga show a remarkable intracellular protection against the oxidative damage (carbonylation) to their proteome (both constitutive and radiation-induced), as compared with their standard species: the bacterium E. coli and the nematode C. elegans [3]. (4) The protective protein antioxidant agent is a small molecule that acts also as a protector of proteins from sensitive speces. (5) When normalized against killing fraction, all four species show the same quantitative correlation with the oxidation of their proteome [4] caused by either gamma or UV irradiation. (6) Protein carbonylation appears as the cause of cellular degeneracy and death, a feature that seems to apply also to human aging and age-related diseases. (7) We propose that Òintrinsic agingÓ - the fundamental chemistry of aging, age-associated diseases, and death - is the progressive oxidation of the cellular proteome leading to its increasing fatal functional degeneracy by the failing of cellular interactome and catalysome.

References:

1: Zahradka K, Slade D, Bailone A, Sommer, S, Averbeck, D, Petranovic, M,

Lindner, AB, & Radman M,_(2006) Nature 443: 569-573

2: Slade D, Lindner AB, Paul G, & Radman M,_(2009) Cell 136: 1044-1055

3: A. Krisko, M. Leroy, M. Radman & M. Meselson, in prep.

4: A. Krisko & M. Radman, in prep.

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