Resistance to Environmental Stress in Drosophila melanogaster Selected for Postponed Senescence

Service, P. M.; Hutchinson, E. W.; MacKinley, M. D.; Rose, M. R.

doi:10.1086/physzool.58.4.30156013

Cited by 299 publications

(91 citation statements)

References 24 publications

(4 reference statements)

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“…Earlier studies have shown that an increase in resistance to stress conditions, including oxidative stress, leads to increase in the lifespan of various organisms, including S. cerevisiae (19,20), Caenorhabditis elegans (21,22), Drosophila melanogaster (23), and mouse (24). Only a few reports, in nonmammalian organisms [(C. elegans (Mev-1) and Drosophila (catalase or superoxide dismutase)], describe hypersensitivity to oxidative stress leading to shortened lifespan (25,26).…”

Section: Discussionmentioning

confidence: 99%

Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

Moskovitz

Barnoy²,

Williams³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

613

504

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Oxidation of proteins by reactive oxygen species is associated with aging, oxidative stress, and many diseases. Although free and protein-bound methionine residues are particularly sensitive to oxidation to methionine sulfoxide derivatives, these oxidations are readily repaired by the action of methionine sulfoxide reductase (MsrA). To gain a better understanding of the biological roles of MsrA in metabolism, we have created a strain of mouse that lacks the MsrA gene. Compared with the wild type, this mutant: (i) exhibits enhanced sensitivity to oxidative stress (exposure to 100% oxygen); (ii) has a shorter lifespan under both normal and hyperoxic conditions; (iii) develops an atypical (tip-toe) walking pattern after 6 months of age; (iv) accumulates higher tissue levels of oxidized protein (carbonyl derivatives) under oxidative stress; and (v) is less able to up-regulate expression of thioredoxin reductase under oxidative stress. It thus seems that MsrA may play an important role in aging and neurological disorders. P rotein-bound methionine residues are among the most susceptible to oxidation by reactive oxygen species (ROS), resulting in formation of methionine sulfoxide [Met(O)] residues. However, this modification can be repaired by methionine sulfoxide reductase (MsrA), which catalyzes the thioredoxindependent reduction of free and protein-bound Met(O) to methionine, both in vitro (1) and in vivo (2). Bacteria and yeast cells lacking the msrA gene show increased sensitivity to oxidative stress and lower survival rates (3, 4), with yeast showing accumulation of high levels of both free and protein-bound Met(O) (2, 4). In addition, overexpression of the MsrA enzyme in human T cells prolongs their life under conditions of oxidative stress (4). Because methionine residues are particularly susceptible to oxidation by ROS, MsrA could have at least three important functions in cellular metabolism: (i) as an antioxidant enzyme that scavenges ROS by facilitating the cyclic interconversion of methionine͞protein-methionine residues between oxidized and reduced forms (2); (ii) as a repair enzyme by keeping critical methionine residues in their reduced form; and (iii) as a regulator of critical enzyme activity through cyclic interconversion of specific methionine residues between oxidized and reduced forms (5, 6). Escherichia coli and Saccharomyces cerevisiae both contain at least two Msrs. One (MsrA) is able to reduce both free and protein-bound Met(O), and the other can reduce only free Met(O). The MsrA protein is highly expressed in liver, kidney, pigment epithelial cells of the retina, macrophages, cerebellum, and brain neurons (7). These tissues͞ cells are sensitive to oxidative stress damages. Therefore, abolishing the MsrA enzyme could lead to loss of antioxidant defense, resulting in enhanced oxidative damage and a decreased lifespan. To investigate the possible role of MsrA as an antioxidant in mammals and its possible influence on lifespan, we created a strain of mouse lacking the MsrA protein. Materials and ...

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Section: Discussionmentioning

confidence: 99%

Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

Moskovitz

Barnoy²,

Williams³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

613

504

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“…Mutations in genes affecting fertility, DNA repair and cellular aging, resistance to environmental stress, and lipid and glycogen content have been associated with altered lifespan and the aging process (12,(27)(28)(29)(30)(31)(32)(33)(34). Candidate loci affecting all of these traits are found in the genomic regions to which QTLs affecting lifespan map (ref.…”

Section: Discussionmentioning

confidence: 99%

“…This question can only be addressed by determining at what loci segregating variation for lifespan occurs in natural populations and by evaluating the distribution of allelic effects at each. Analyses of physiological correlates of longevity in Drosophila lines selected for postponed senescence have implicated loci involved in stress response and lipid biosynthesis in the selection response (12,(28)(29)(30)(31)(32). Additional candidate loci associated with the aging process are those affecting somatic mutation rate and cellular aging (27,(33)(34)(35)(36).…”

mentioning

confidence: 99%

Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster

Nuzhdin

Pasyukova

Dilda

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

313

267

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Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms. Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life. Analyses of Drosophila spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late-age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis. The QTLs had large sex-specific effects on lifespan and agespecific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects. Late ageof-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan.

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“…Remarkably these lines show greater resistance to environmental stress (Service et al 1985). Of the many mutations known to lengthening life span in the nematode Caenorhabditis elegans, those aecting general metabolic rates (e.g.…”

Section: Introductionmentioning

confidence: 99%

Increasing Saccharomyces cerevisiae stress resistance, through the overactivation of the heat shock response resulting from defects in the Hsp90 chaperone, does not extend replicative life span but can be associated with slower chronological ageing of nondividing cells

et al. 2001

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Recent studies on Drosophila and Caenorhabditis elegans indicate that increases in stress resistance result in a longer chronological life span, an effect that must operate primarily on the postmitotic tissues of the adult. Stress resistance can be increased through decreases in Hsp90 chaperone activity, since Hsp90 acts to downregulate the activity of heat shock transcription factor. This study investigated whether the increases in stress resistance associated with reduced Hsp90 chaperone activity influence ageing in the budding yeast Saccharomyces cerevisiae, ageing being measured either as the replicative (nonchronological) senescence of budding cells or as the chronological ageing of non-dividing (stationary phase) cultures. Overactivation of the heat shock response caused no slowing of replicative senescence. In some situations though it was associated with a longer chronological life span of stationary cells, the yeast equivalent of the postmitotic state. This is consistent with the idea that stress resistance exerts its life span-extending effects primarily in postmitotic cells and tissues.

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Resistance to Environmental Stress in Drosophila melanogaster Selected for Postponed Senescence

Cited by 299 publications

References 24 publications

Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster

Increasing Saccharomyces cerevisiae stress resistance, through the overactivation of the heat shock response resulting from defects in the Hsp90 chaperone, does not extend replicative life span but can be associated with slower chronological ageing of nondividing cells

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