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. 2005 Dec 31;27(3):183–199. doi: 10.1007/s11357-005-2915-0

Oxidative damage, aging and anti-aging strategies

Ronny Haenold 1, D Mokhtar Wassef 1, Stefan H Heinemann 2, Toshinori Hoshi 1,✉
PMCID: PMC3458494  PMID: 23598652

Abstract

The last two decades brought remarkable insight into the nature of normal aging in multicellular organisms. However, we are still far away from realizing extension of maximum lifespan in humans. An important modulator of lifespan is oxidative damage induced by reactive species, such as reactive oxygen species (ROS). Studies from yeast, Caenorhabditis and Drosophila primarily focused on (1) reduced generation or (2) elimination of ROS but have two principal shortcomings: (1) dietary restriction and single gene mutations are often associated with physiological impairments and (2) overexpression of components of the antioxidant system extend lifetime only under stress-induced conditions. Recent results from Drosophila indicate the involvement of an endogenous repair and elimination system for oxidatively damaged proteins in the process of aging. This system includes methionine sulfoxide reductase A (MSRA) and the carbonyl reductase Sniffer, the protein-ubiquitin ligase Parkin and the chaperone Hsp22. In this review we summarize different anti-aging strategies and discuss a synergistic interaction between protection against free radicals and specific repair/elimination of oxidative damage in lifespan extension primarily using the model system Drosophila. To achieve lifespan extension, available experiments are often methodically grouped into (1) caloric restriction, (2) single gene mutation, and (3) overexpression of genes. Here we summarize different strategies by a more causal classification: (1) prevention of ROS generation, (2) reducing free ROS level, and (3) repair and elimination of ROS-damaged proteins.

Key words: antioxidant system, Drosophila, methionine sulfoxide reductases, oxidative stress theory of aging, protein oxidation, ROS

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Abbreviations

CR

caloric restriction

met-O

methionine sulfoxide

MSRA/B

methionine sulfoxide reductases A/B

ROS

reactive oxygen species

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