Living on the edge: stress and activation of stress responses promote lifespan extension.
Oxidative stress constitutes the basis of physio-pathological situations such as neurodegenerative diseases and aging. However, sublethal exposure to toxic molecules such as reactive oxygen species can induce cellular responses that result in stress fitness. Studies in Schizosaccharomyces pombe have recently showed that the Sty1 MAP kinase, known to be activated by hydrogen peroxide and other cellular stressors, plays a pivotal role in promoting fitness and longevity when it becomes activated by calorie restriction, a situation which induces oxidative metabolism and reactive oxygen species production. Activation of the MAP kinase by calorie restriction during logarithmic growth induces a transcriptional anti-stress response including genes essential to promote lifespan extension. Importantly enough, the lifespan promotion exerted by deletion of the pka1 or sck2 genes, inactivating the two main nutrient-responsive pathways, is dependent on the presence of a functional Sty1 stress pathway, since double mutants also lacking Sty1 or its main substrate Atf1 do not display extended viability. In this Research Perspective, we review these findings in relation to previous reports and extend important aspects of the original study. We propose that moderate stress levels that are not harmful for cells can make them stronger.
Zuin
Alice
A
Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Castellano-Esteve
David
D
Ayté
José
J
Hidalgo
Elena
E
D000375:Aging; D006801:Humans; D008136:Longevity; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism
D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases
Free Radic Biol Med. 2007 Aug 15;43(4):477-503
17640558
Biol Chem. 2006 Oct-Nov;387(10-11):1357-61
17081107
Eukaryot Cell. 2008 Jul;7(7):1127-35
18469137
PLoS Genet. 2009 Mar;5(3):e1000408
19266076
J Cell Sci. 1996 Jun;109 ( Pt 6):1347-57
8799823
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70
19433800
Mol Cell Biol. 2000 Sep;20(17):6426-34
10938120
Genes Dev. 1995 Sep 1;9(17):2117-30
7657164
Genes Dev. 1996 Sep 15;10(18):2289-301
8824588
Mol Biol Cell. 2003 Jan;14(1):214-29
12529438
Aging (Albany NY). 2009 Apr 20;1(4):357-62
20157523
Biochem Soc Trans. 2005 Feb;33(Pt 1):257-60
15667320
Nat Rev Genet. 2007 Nov;8(11):835-44
17909538
PLoS Genet. 2008 Jan;4(1):e13
18225956
FEBS Lett. 2005 Dec 19;579(30):6809-13
16336970
J Cell Sci. 2009 May 1;122(Pt 9):1418-29
19366728
Mech Ageing Dev. 2006 Nov;127(11):849-61
17002888
Mol Genet Genomics. 2006 Dec;276(6):495-502
17043891
Ann N Y Acad Sci. 2006 May;1067:343-8
16804009
Mol Cell. 2007 Apr 13;26(1):1-14
17434122
Curr Med Chem. 2009;16(10):1229-35
19355881
Cell Metab. 2008 Mar;7(3):200-3
18316025
Genes Dev. 1996 Sep 15;10(18):2276-88
8824587
Science. 2001 Apr 13;292(5515):288-90
11292860
Cell Metab. 2007 Oct;6(4):280-93
17908557
Trends Cell Biol. 2009 Dec;19(12):705-15
19833516
EMBO J. 2010 Mar 3;29(5):981-91
20075862
EMBO J. 1995 Dec 15;14(24):6193-208
8557039
Aging Cell. 2006 Aug;5(4):345-57
16822282
Genes Dev. 1991 Apr;5(4):561-71
1849107
PLoS Genet. 2007 May 25;3(5):e84
17530929
Ann N Y Acad Sci. 2007 Nov;1119:112-21
18056960
Mol Biol Cell. 2008 Jan;19(1):308-17
18003976
Nature. 1995 Dec 14;378(6558):739-43
7501024