Abstract
Longevity is a highly malleable trait which is influenced by many genetic and environmental factors including nutrition. Mild stress of dietary restriction (DR) is often beneficial by extending longevity in many organisms. Here, DR-induced effects on longevity were tested for genetic variation in a set of recombinant inbred lines (RIL) in D. melanogaster. Genetic variability was significant in the longevity response following a DR-treatment across RIL, with detrimental effects in several RIL but beneficial effects in other RIL. One quantitative trait locus (QTL) was consistently significant in the middle of chromosome 2 for DR-induced changes in longevity, including hormesis (an increase in longevity by DR). Another QTL co-localized with a previously found QTL for starvation resistance in females. Several other QTL were also significant on most chromosomal arms. Longevity in controls was negatively correlated to DR effects across RIL for longevity in females, the sex showing higher DR-induced hormesis. This negative genetic correlation highlights the importance to further investigate the effects of genetic variation in the strength of DR-induced hormesis in longevity and its sex-specificity.
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References
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390–392. https://doi.org/10.1126/science.1099196
Defays R, Gómez FH, Sambucetti P, Scannapieco AC, Loeschcke V, Norry FM (2011) Quantitative trait loci for longevity in heat-stressed Drosophila melanogaster. Exp Gerontol 46:819–826
Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics, 4th edn. Prentice Hall, London
FlyBase Consortium (2003) The FlyBase database of the Drosophila genome projects and community literature. Nucleic Acids Res 31:172–175
Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328:321–326. https://doi.org/10.1126/science.1172539
Gasser SCM (2001) The molecular biology of the SIR proteins. Gene 279:1–16
Gomez FH, Bertoli CI, Sambucetti P, Scannapieco AC, Norry FM (2009) Heat induced hormesis in longevity as correlated response to thermal-stress selection in Drosophila buzzatii. J Therm Biol 34:17–22
Gomez FH, Sambucetti P, Norry FM (2016) Elevated extension of longevity by cyclically heat stressing a set of recombinant inbred lines of Drosophila melanogaster throughout their adult life. Biogerontology 17:883–892. https://doi.org/10.1007/s10522-016-9658-4
Haigis MC, Sinclair DA (2010) Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 5:253–295
Hansen M, Taubert S, Crawford D, Libina N, Lee S-J, Kenyon C (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6:95–110
Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4:e24. https://doi.org/10.1371/journal.pgen.0040024
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395
Heilbronn LK, Civitarese AE, Bogacka I, Smith SR, Hulver M, Ravussin E (2005) Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting. Obes Res 13:574–581
Hekimi S, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354
Hercus MJ, Loeschcke V, Rattan SIS (2003) Lifespan extension of Drosophila melanogaster through hormesis by repeated mild heat stress. Biogerontology 4:149–156
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196
Kaeberlein M, Powers RW, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310:1193–1196
Kaeberlein M et al (2006) Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell 5:487–494. https://doi.org/10.1111/j.1474-9726.2006.00238.x
Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885–890
Kenyon C (2001) A conserved regulatory system for aging. Cell 105:165–168
Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 105:449–460. https://doi.org/10.1016/j.cell.2005.02.002
Kim H-J et al (2010) Gene expression profiling implicates OXPHOS complexes in lifespan extension of flies over-expressing a small mitochondrial chaperone, Hsp22. Exp Gerontol 45:611–620. https://doi.org/10.1016/j.exger.2009.12.012
Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120:437–447. https://doi.org/10.1016/j.cell.2005.01.027
Krittika S, Yadav P (2019) An overview of two decades of diet restriction studies using Drosophila. Biogerontology 20:723–740. https://doi.org/10.1007/s10522-019-09827-0
Le Bourg E (2009) Hormesis, aging, and longevity. Biochim Biophys Acta 1790:1030–1039. https://doi.org/10.1016/j.bbagen.2009.01.004
Le Bourg E (2018) Does calorie restriction in primates increase lifespan? Revisiting studies on macaques (Macaca mulatta) and mouse lemurs (Microcebus murinus). BioEssays 40:1800111. https://doi.org/10.1002/bies.201800111
Le Bourg E, Rattan SIS (2006) Can dietary restriction increase longevity in all species, particularly in human beings? Introduction to a debate among experts. Biogerontology 7:123–125
Le Bourg E, Rattan SIS (eds) (2008) Mild stress and healthy aging: applying hormesis in aging research and interventions. Springer, Dordrecht
Lee C, Longo V (2016) Dietary restriction with and without caloric restriction for healthy aging. F1000Research 5(F1000 Faculty Rev):117. https://doi.org/10.12688/f1000research.7136.1
Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128
Longo VD, Fabrizio P (2002) Regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans? Cell Mol Life Sci 59:903–908
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Sinauer, Sunderland
Mackay TFC (2001) Quantitative trait loci in Drosophila. Nat Rev Genet 2:11–20
Mair W, Dillin A (2008) Aging and survival: the genetics of life span extension by dietary restriction. Ann Rev Biochem 77:727–754
Masoro EJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126:913–922. https://doi.org/10.1016/j.mad.2005.03.012
Matai L, Sarkar GC, Chamoli M et al (2019) Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis. Proc Natl Am Sci USA 116:17383–17392
Minois N (2000) Longevity and aging: beneficial effect of exposure to mild stress. Biogerontology 1:15–29
Moskalev AA, Plyusnina EN, Shaposhnikov MV (2011) Radiation hormesis and radioadaptive response in Drosophila melanogaster flies with different genetic backgrounds: the role of cellular stress-resistance mechanisms. Biogerontology 12:253–263. https://doi.org/10.1007/s10522-011-9320-0
Motta MC, Divecha N, Lemieux M, et al (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–56
Norry FM, Scannapieco AC, Sambucetti P, Bertoli CI, Loeschcke V (2008) QTL for the thermotolerance effect of heat hardening, knockdown resistance to heat and chill-coma recovery in an intercontinental set of recombinant inbred lines of Drosophila melanogaster. Mol Ecol 17:4570–4581
Parsons PA (2002) Radiation hormesis: challenging LNT theory via ecological and evolutionary considerations. Health Phys 82:513–516. https://doi.org/10.1097/00004032-200204000-00011
Partridge L, Pletcher SD, Mair W (2005) Dietary restriction, mortality trajectories, risk and damage. Mech Ageing Dev 126:35–41
Piper MDW, Skorupa D, Partridge L (2005) Diet, metabolism and lifespan in Drosophila. Exp Gerontol 40:857–862. https://doi.org/10.1016/j.exger.2005.06.013
Rattan SIS (2008) Hormesis in aging. Ageing Res Rev 7:63–78. https://doi.org/10.1016/j.arr.2007.03.002
Rattan SIS (2014) Molecular gerontology: from homeodynamics to hormesis. Curr Pharm Des 20:3036–3039. https://doi.org/10.2174/13816128113196660708
Rattan SIS, Demirovic D, Nizard C (2018) A preliminary attempt to establish multiple stress response profiles of human skin fibroblasts exposed to mild or severe stress during ageing in vitro. Mech Age Dev 170:92–97. https://doi.org/10.1016/j.mad.2017.09.005
Rice WR (1989) Analyzing tables of statistical tests. Evolution 43:223–225
Sambucetti P, Loeschcke V, Norry FM (2015) Patterns of longevity and fecundity at two temperatures in a set of heat-selected recombinant inbred lines of Drosophila melanogaster. Biogerontology 16(6):801–810. https://doi.org/10.1007/s10522-015-9606-8
Sarup P, Petersen SMM, Nielsen NC, Loeschcke V, Malmendal A (2016) Mild heat treatments induce long-term changes in metabolites associated with energy metabolism in Drosophila melanogaster. Biogerontology 17:873–882
Sørensen JG, Nielsen MM, Loeschcke V (2007) Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors. J Evol Biol 20:1624–1636
Sørensen JG, Sarup P, Kristensen TN, Loeschcke V (2008) Temperature-induced hormesis in Drosophila. In: Le Bourg E, Rattan SIS (eds) Mild stress and healthy aging. Springer, Dordrecht
Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK (2009) The TOR pathway comes of age. Biochim Biophys Acta 1790:1067–1074
StatSoft (1999) STATISTICA for Windows. Computer Program Manual. StatSoft Inc., Tulsa
Tatar M (2011) The plate half-full: status of research on the mechanisms of dietary restriction in Drosophila melanogaster. Exp Gerontol 5:363–368
Tower J (2009) Hsp and aging. Trends Endocrinol Metab 20:216–222
Tower J (2011) Heat-shock proteins and Drosophila aging. Exp Gerontol 46:355–362
Tower J (2017) Sex-specific gene expression and life span regulation. Trends Endocrinol Metab 28:735–747
Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Müller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620
Wang SC, Basten J, Zeng Z-B (2010) Windows QTL Cartographer 2.5. Department of Statistics. North Carolina State University, Raleigh, NC
White TCR (1993) The inadequate environment: nitrogen and the abundance of animals. Springer, Berlin
Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689
Zeng Z-B (1994) Precision mapping of quantitative trait loci. Genetics 136:1457–1468
Acknowledgements
This work was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (Grant No. CONICET, PIP11220130100083CO) and grants from Agencia Nacional de Promoción Científica y Tecnológica (Grant No. ANPCyT, PICT-2017-1426) and Universidad de Buenos Aires to FMN.
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Gomez, F.H., Stazione, L., Sambucetti, P. et al. Negative genetic correlation between longevity and its hormetic extension by dietary restriction in Drosophila melanogaster. Biogerontology 21, 191–201 (2020). https://doi.org/10.1007/s10522-019-09852-z
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DOI: https://doi.org/10.1007/s10522-019-09852-z