Skip to main content

Aging: Reading, Reasoning, and Resolving Using Drosophila as a Model System

  • Chapter
  • First Online:
Models, Molecules and Mechanisms in Biogerontology

Abstract

Aging is a complex process, involving both genetic and environmental factors, and can be defined as the time-dependent deterioration of the physiological and cellular functions necessary for survival and fertility. Some irretrievable series of biological changes occur during this phenomenon that inevitably results in the death of the organism. Although the exact cause of these changes is still unresolved and completely unrelated in different cases entailing no common mechanism, yet they often indicate a shared element of descent. Because of this mysterious behavior, aging process is still on the frontier of biomedical research and investigators are still trying to unravel the ambiguities of this phenomenon. The last few decades have shown remarkable improvement in the genetic analysis of aging, with a greater prominence near interpretation of molecular mechanisms, pathways, and physiological processes associated with longevity. Since limitations associated with human genetics do not permit identification or analysis of candidate gene(s) and pathway(s) and detailed comprehensive mechanistic studies, given the fact that the basic biological processes remain conserved throughout phylogeny from archaea to multicellular organism, model organisms allow easier execution of such studies. Therefore, utilization of model organisms for modifier screening and deciphering different aspects of aging phenomenon has emerged as a prime approach to study the details of aging. Out of several conventional model organisms, Drosophila melanogaster has emerged as an excellent system to interpret vital genetic/cellular molecular pathways of human aging, due to several advantageous characteristics including its short lifespan, short generation time, availability of powerful genetic tools, and conserved homology. Numerous key cellular events and pathways as well as drug discoveries have been untangled by exploiting Drosophila as a system of aging research. Thus, this chapter attempts to provide a brief outline of the role of Drosophila in understanding and easing out aging studies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ables GP, Brown-Borg HM, Buffenstein R, Church CD, Elshorbagy AK, Gladyshev VN, Huang TH, Miller RA, et al. The first international mini-symposium on methionine restriction and lifespan. Front Genet. 2014;5:122.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, et al. The genome sequence of Drosophila melanogaster. Science. 2000;287:2185–95.

    Article  PubMed  Google Scholar 

  3. Akerfelt M, Morimoto RI, Sistonen L. Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol. 2010;11:545–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Anantharaju A, Feller A, Chedid A. Aging liver. A review. Gerontology. 2002;48:343–53.

    Article  CAS  PubMed  Google Scholar 

  5. Anisimov VN. Metformin: do we finally have an anti-aging drug? Cell Cycle. 2013;12:3483–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Antico Arciuch VG, Elguero ME, Poderoso JJ, Carreras MC. Mitochondrial regulation of cell cycle and proliferation. Antioxid Redox Signal. 2012;16:1150–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Arking R. Biology of aging: observations and principles. 3rd ed. Prentice Hall: Englewood Cliffs; 1991.

    Google Scholar 

  8. Arking R, Buck S, Berrios A, Dwyer S, Baker GT 3rd. Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila. Dev Genet. 1991;12:362–70.

    Article  CAS  PubMed  Google Scholar 

  9. Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet. 2012;13:693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Armanios M, Alder JK, Parry EM, Karim B, Strong MA, Greider CW. Short telomeres are sufficient to cause the degenerative defects associated with aging. Am J Hum Genet. 2009;85:823–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Arslan MA, Csermely P, Soti C. Protein homeostasis and molecular chaperones in aging. Biogerontology. 2006;7:383–9.

    Article  CAS  PubMed  Google Scholar 

  12. Bales CW, Kraus WE. Caloric restriction: implications for human cardiometabolic health. J Cardiopulm Rehabil Prev. 2013;33:201–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Barnes AI, Wigby S, Boone JM, Partridge L, Chapman T. Feeding, fecundity and lifespan in female Drosophila melanogaster. Proc Biol Sci. 2008;275:1675–83.

    PubMed  PubMed Central  Google Scholar 

  14. Bauer JH, Morris SN, Chang C, Flatt T, Wood JG, Helfand SL. dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in D. melanogaster. Aging (Albany NY). 2009;1:38–48.

    Google Scholar 

  15. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bayliak MM, Lushchak VI. The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistance in yeast Saccharomyces cerevisiae. Phytomedicine. 2011;18:1262–8.

    Article  PubMed  Google Scholar 

  17. Ben-Avraham D, Muzumdar RH, Atzmon G. Epigenetic genome-wide association methylation in aging and longevity. Epigenomics. 2012;4:503–9.

    Article  CAS  PubMed  Google Scholar 

  18. Benayoun BA, Pollina EA, Brunet A. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat Rev Mol Cell Biol. 2015;16:593–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Biteau B, Karpac J, Hwangbo D, Jasper H. Regulation of Drosophila lifespan by JNK signaling. Exp Gerontol. 2011;46:349–54.

    Article  CAS  PubMed  Google Scholar 

  20. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Mechanisms of lifespan extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007;3:640–9.

    Article  CAS  PubMed  Google Scholar 

  22. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279:349–52.

    Article  CAS  PubMed  Google Scholar 

  23. Bokov A, Chaudhuri A, Richardson A. The role of oxidative damage and stress in aging. Mech Ageing Dev. 2004;125:811–26.

    Article  CAS  PubMed  Google Scholar 

  24. Boonekamp JJ, Simons MJ, Hemerik L, Verhulst S. Telomere length behaves as biomarker of somatic redundancy rather than biological age. Aging Cell. 2013;12:330–2.

    Article  CAS  PubMed  Google Scholar 

  25. Boutros M, Agaisse H, Perrimon N. Sequential activation of signaling pathways during innate immune responses in Drosophila. Dev Cell. 2002;3:711–22.

    Article  CAS  PubMed  Google Scholar 

  26. Brand MD. The sites and topology of mitochondrial superoxide production. Exp Gerontol. 2010;45:466–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993;118:401–15.

    Article  CAS  PubMed  Google Scholar 

  28. Branson K, Robie AA, Bender J, Perona P, Dickinson MH. High-throughput ethomics in large groups of Drosophila. Nat Methods. 2009;6:451–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A. 2005;102:3105–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, Zhang D, Scadden DT, et al. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013;3:319–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD, Hoddinott M, Sutphin GL, et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477:482–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Burtner CR, Kennedy BK. Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol. 2010;11:567–78.

    Article  CAS  PubMed  Google Scholar 

  33. Cabanillas R, Cadinanos J, Villameytide JA, Perez M, Longo J, Richard JM, Alvarez R, Duran NS, et al. Nestor-Guillermo progeria syndrome: a novel premature aging condition with early onset and chronic development caused by BANF1 mutations. Am J Med Genet A. 2011;155A:2617–25.

    Article  PubMed  CAS  Google Scholar 

  34. Cao K, Blair CD, Faddah DA, Kieckhaefer JE, Olive M, Erdos MR, Nabel EG, Collins FS. Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest. 2011;121:2833–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Casillas MA Jr, Lopatina N, Andrews LG, Tollefsbol TO. Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically transformed human fibroblasts. Mol Cell Biochem. 2003;252:33–43.

    Article  CAS  PubMed  Google Scholar 

  36. Castillo-Quan JI, Li L, Kinghorn KJ, Ivanov DK, Tain LS, Slack C, Kerr F, Nespital T, et al. Lithium promotes longevity through GSK3/NRF2-dependent hormesis. Cell Rep. 2016;15:638–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979;59:527–605.

    Article  CAS  PubMed  Google Scholar 

  38. Chanu SI, Sarkar S. Targeted downregulation of dMyc suppresses pathogenesis of human neuronal tauopathies in Drosophila by limiting heterochromatin relaxation and Tau hyperphosphorylation. Mol Neurobiol. 2017;54:2706–19.

    Article  CAS  PubMed  Google Scholar 

  39. Chapman T, Partridge L. Female fitness in Drosophila melanogaster: an interaction between the effect of nutrition and of encounter rate with males. Proc R Soc Lond Ser B. 1996;263:755–9.

    Article  CAS  Google Scholar 

  40. Chen W, White MA, Cobb MH. Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway. J Biol Chem. 2002;277:49105–10.

    Article  CAS  PubMed  Google Scholar 

  41. Ching TT, Chiang WC, Chen CS, Hsu AL. Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity. Aging Cell. 2011;10:506–19.

    Article  CAS  PubMed  Google Scholar 

  42. Chippindale AK, Leroi AM, Kim SB, Rose MR. Phenotypic plasticity and selection in Drosophila life-history evolution. I. Nutrition and the cost of reproduction. J Evol Biol. 1993;6:171–93.

    Article  Google Scholar 

  43. Cho J, Hur JH, Walker DW. The role of mitochondria in Drosophila aging. Exp Gerontol. 2011;46:331–4.

    Article  CAS  PubMed  Google Scholar 

  44. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104–6.

    Article  CAS  PubMed  Google Scholar 

  45. Clark AM, Gould AB. Genetic control of adult lifespan in Drosophila melanogaster. Exp Gerontol. 1970;15:157–62.

    Article  Google Scholar 

  46. Collins JJ, Evason K, Pickett CL, Schneider DL, Kornfeld K. The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan. PLoS Genet. 2008;4:e1000230.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Conley KE, Jubrias SA, Esselman PC. Oxidative capacity and ageing in human muscle. J Physiol. 2000;526:203–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cummings CJ, Sun Y, Opal P, Antalffy B, Mestril R, Orr HT, Dillmann WH, Zoghbi HY. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum Mol Genet. 2001;10:1511–8.

    Article  CAS  PubMed  Google Scholar 

  49. Curtis C, Landis GN, Folk D, Wehr NB, Hoe N, Waskar M, Abdueva D, Skvortsov D, et al. Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome Biol. 2007;8:R262.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Danilov A, Shaposhnikov M, Shevchenko O, Zemskaya N, Zhavoronkov A, Moskalev A. Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity. Oncotarget. 2015;6:19428–44.

    Article  PubMed  PubMed Central  Google Scholar 

  51. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055.

    Article  PubMed  Google Scholar 

  52. Dechat T, Pfleghaar K, Sengupta K, Shimi T, Shumaker DK, Solimando L, Goldman RD. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 2008;22:832–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature. 2007;448:151–6.

    Article  CAS  PubMed  Google Scholar 

  54. Dröge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol. 2002;371:333–1345.

    Google Scholar 

  55. Dudas SP, Arking R. A coordinate upregulation of antioxidant gene activities is associated with the delayed onset of senescence in a long-lived strain of Drosophila. J Gerontol A Biol Sci Med Sci. 1995;50:B117–27.

    Article  CAS  PubMed  Google Scholar 

  56. Efeyan A, Zoncu R, Sabatini DM. Amino acids and mTORC1: from lysosomes to disease. Trends Mol Med. 2012;18:524–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Eisenberg T, Knauer H, Schauer A, Beuttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11:1305–14.

    Article  CAS  PubMed  Google Scholar 

  58. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003;423:293–8.

    Article  CAS  PubMed  Google Scholar 

  59. Espada J, Varela I, Flores I, Ugalde AP, Cadinanos J, Pendas AM, Stewart CL, Tryggvason K, et al. Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J Cell Biol. 2008;181:27–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene. 2002;21:5427–40.

    Article  CAS  PubMed  Google Scholar 

  61. Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, Lin SZ, Harn HJ. Polyglutamine (PolyQ) diseases: genetics to treatments. Cell Transplant. 2014;23:441–8.

    Article  PubMed  Google Scholar 

  62. Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, SenGupta T, Nilsen H, Mitchell JR, Croteau DL, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014;157:882–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fang EF, Scheibye-Knudsen M, Chua KF, Mattson MP, Croteau DL, Bohr VA. Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol. 2016;17:308–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ferguson M, Mockett RJ, Shen Y, Orr WC, Sohal RS. Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster. Biochem J. 2005;390:501–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Finkel T, Holbrook NJ. Oxidants, oxidative stress and biology of ageing. Nature. 2000;408:239–47.

    Article  CAS  PubMed  Google Scholar 

  66. Flatt T. Survival costs of reproduction in Drosophila. Exp Gerontol. 2011;46:369–75.

    Article  PubMed  Google Scholar 

  67. Flatt T. A new definition of aging? Front Genet. 2012;3:148.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Fleming JE, Walton JK, Dubitsky R, Bensch KG. Aging results in an unusual expression of Drosophila heat shock proteins. Proc Natl Acad Sci U S A. 1988;85:4099–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015;161:106–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet. 2007;23:413–8.

    Article  CAS  PubMed  Google Scholar 

  71. Gardner TS. The use of Drosophila melanogaster as a screening agent for longevity factors II. The effects of biotin, pyridoxine, sodium yeast nucleate, and pantothenic acid on the lifespan of the fruit fly. J Gerontol. 1948;3:9–13.

    Article  CAS  PubMed  Google Scholar 

  72. Gargano JW, Martin I, Bhandari P, Grotewiel MS. Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila. Exp Gerontol. 2005;40:386–95.

    Article  PubMed  Google Scholar 

  73. Gems D, Partridge L. Insulin/IGF signalling and ageing: seeing the bigger picture. Curr Opin Genet Dev. 2001;11:287–92.

    Article  CAS  PubMed  Google Scholar 

  74. Geuking P, Narasimamurthy R, Lemaitre B, Basler K, Leulier F. A non-redundant role for Drosophila Mkk4 and hemipterous/Mkk7 in TAK1-mediated activation of JNK. PLoS One. 2009;4:e7709.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Giannakou ME, Goss M, Jünger MA, Hafen E, Leevers SJ, Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science. 2004;305:361.

    Google Scholar 

  76. Gong WJ, Golic KG. Loss of Hsp70 in Drosophila is pleiotropic, with effects on thermotolerance, recovery from heat shock and neurodegeneration. Genetics. 2006;172:275–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Gonzalez-Suarez I, Redwood AB, Perkins SM, Vermolen B, Lichtensztejin D, Grotsky DA, MorgadoPalacin L, Gapud EJ, et al. Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J. 2009;28:2414–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Grammatikakis I, Panda AC, Abdelmohsen K, Gorospe M. Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging. Aging. 2014;6:992–1009.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985;43:405–13.

    Article  CAS  PubMed  Google Scholar 

  80. Gronke S, Clarke DF, Broughton S, Andrews TD, Partridge L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 2010;6:e1000857.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Grotewiel MS, Martin I, Bhandari P, Cook-Wiens E. Functional senescence in Drosophila melanogaster. Aging Res Rev. 2005;4:372–97.

    Article  CAS  Google Scholar 

  82. Grover D, Yang J, Ford D, Tavaré S, Tower J. Simultaneous tracking of movement and gene expression in multiple Drosophila melanogaster flies using GFP and DsRED fluorescent reporter transgenes. BMC Res Notes. 2009;2:58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Guarente L. Calorie restriction and sirtuins revisited. Genes Dev. 2013;27:2072–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature. 2000;408:255–62.

    Article  CAS  PubMed  Google Scholar 

  85. Guha S, Cao M, Kane RM, Savino AM, Zou S, Dong Y. The longevity effect of cranberry extract in Caenorhabditis elegans is modulated by daf-16 and osr-1. Age (Dordr). 2013;35:1559–74.

    Article  Google Scholar 

  86. Guillozet AL, Weintraub S, Mash DC, Mesulam MM. Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch Neurol. 2003;60:729–36.

    Article  PubMed  Google Scholar 

  87. Guo L, Karpac J, Tran SL, Jasper H. PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell. 2014;156:109–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Haigis MC, Yankner BA. The aging stress response. Mol Cell. 2010;40:333–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Han S, Brunet A. Histone methylation makes its mark on longevity. Trends Cell Biol. 2012;22:42–9.

    Article  PubMed  CAS  Google Scholar 

  90. Hands S, Sinadinos C, Wyttenbach A. Polyglutamine gene function and dysfunction in the ageing brain. Biochim Biophys Acta. 2008;1779:507–21.

    Article  CAS  PubMed  Google Scholar 

  91. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49:359–67.

    Article  CAS  PubMed  Google Scholar 

  92. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11:298–300.

    Article  CAS  PubMed  Google Scholar 

  93. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Harshman LG, Haberer BA. Oxidative stress resistance: a robust correlated response to selection in extended longevity lines of Drosophila melanogaster. J Gerontol A Biol Sci Med Sci. 2000;55:B415–7.

    Article  CAS  PubMed  Google Scholar 

  95. Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature. 2011;475:324–32.

    Article  CAS  PubMed  Google Scholar 

  96. Hass BS, Hart RW, Lu MH, Lyn-Cook BD. Effects of caloric restriction in animals on cellular function, oncogene expression, and DNA methylation in vitro. Mutat Res. 1993;295:281–9.

    Article  CAS  PubMed  Google Scholar 

  97. Hayflick L. The biology of human aging. Plast Reconstr Surg. 1981;67:536–50.

    Article  CAS  PubMed  Google Scholar 

  98. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.

    Article  CAS  PubMed  Google Scholar 

  99. He Y, Jasper H. Studying aging in Drosophila. Methods. 2014;68:129–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. He X, Liu RH. Cranberry phytochemicals: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem. 2006;54:7069–74.

    Article  CAS  PubMed  Google Scholar 

  101. He C, Tsuchiyama SK, Nguyen QT, Plyusnina EN, Terrill SR, Sahibzada S, Patel B, Faulkner AR, et al. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import. PLoS Genet. 2014;10:e1004860.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Helfand SL, Rogina B. Genetics of aging in the fruit fly, Drosophila melanogaster. Annu Rev Genet. 2003a;37:329–48.

    Article  CAS  PubMed  Google Scholar 

  103. Helfand SL, Rogina B. From genes to aging in Drosophila. Adv Genet. 2003b;49:67–109.

    Article  CAS  PubMed  Google Scholar 

  104. Herman MM, Miquel J, Johnson M. Insect brain as a model for study of aging. Age-related changes in Drosophila melanogaster. Acta Neuropathol. 1971;19:167–83.

    Article  CAS  PubMed  Google Scholar 

  105. Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.

    Article  CAS  PubMed  Google Scholar 

  106. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–7.

    Article  CAS  PubMed  Google Scholar 

  107. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Howell AB. Bioactive compounds in cranberries and their role in prevention of urinary tract infections. Mol Nutr Food Res. 2007;51:732–7.

    Article  CAS  PubMed  Google Scholar 

  109. Huey RB, Suess J, Hamilton H, Gilchrist GW. Starvation resistance in Drosophila melanogaster: testing for a possible ‘cannibalism’ bias. Funct Ecol. 2004;18:952–4.

    Article  Google Scholar 

  110. Hutchinson EW, Shaw AJ, Rose MR. Quantitative genetics of postponed aging in Drosophila melanogaster. II Analysis of selected lines. Genetics. 1991;127:729–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Hwangbo DS, Gershman B, Tu MP, Palmer M, Tatar M. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature. 2004;429:562–6.

    Article  CAS  PubMed  Google Scholar 

  112. Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN. Conserved microRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell. 2009;139:1096–108.

    Article  CAS  PubMed  Google Scholar 

  113. Igaki T. Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling. Apoptosis. 2009;14:1021–8.

    Article  PubMed  Google Scholar 

  114. Iliadi KG, Boulianne GL. Age-related behavioral changes in Drosophila. Ann N Y Acad Sci. 2010;1197:9–18.

    Article  PubMed  Google Scholar 

  115. Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R. Calorie restriction mimetics: an emerging research field. Aging Cell. 2006;5:97–108.

    Article  CAS  PubMed  Google Scholar 

  116. Ja WW, Carvalho GB, Mak EB, de la Rosa NN, Fang AY, Liong JC, Brummel T, Benzer S. Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A. 2007;104:8253–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Jafari M. Drosophila melanogaster as a model system for the evaluation of anti-aging compounds. Fly (Austin). 2010;4:253–7.

    Article  CAS  Google Scholar 

  118. Jafari M, Felgner JS, Bussel II, Hutchili T, Khodayari B, Rose MR, Vince-Cruz C, Mueller LD. Rhodiola: a promising anti-aging Chinese herb. Rejuvenation Res. 2007;10:587–602.

    Article  PubMed  Google Scholar 

  119. Jafari M, Zarban A, Pham S, Wang T. Rosa damascena decreased mortality in adult Drosophila. J Med Food. 2008;11:9–13.

    Article  CAS  PubMed  Google Scholar 

  120. Jain S, Thakkar N, Chhatai J, Bhadra MP, Bhadra U. Long non-coding RNA: functional agent for disease traits. RNA Biol. 2016;16:1–14.

    Google Scholar 

  121. Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, et al. Histone demethylase UTX-1 regulates C. elegans lifespan by targeting the insulin/IGF-1 signaling pathway. Cell Metab. 2011;14:161–72.

    Article  CAS  PubMed  Google Scholar 

  122. Johnson GL, Nakamura K. The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. Biochim Biophys Acta. 2007;1773:1341–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Jones MA, Grotewiel M. Drosophila as a model for age-related impairment in locomotor and other behaviors. Exp Gerontol. 2011;46:320–5.

    Article  PubMed  Google Scholar 

  124. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004;14:885–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Karpac J, Jasper H. Insulin and JNK: optimizing metabolic homeostasis and lifespan. Trends Endocrinol Metab. 2009;20:100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Kato M, Chen X, Inukai S, Zhao H, Slack FJ. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans. RNA. 2011;17:1804–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Kenyon CJ. The genetics of ageing. Nature. 2010;464:504–12.

    Article  CAS  PubMed  Google Scholar 

  128. Kim J, Kim KM, Noh JH, Yoon JH, Abdelmohsen K, Gorospe M. Long noncoding RNAs in diseases of aging. Biochim Biophys Acta. 2016;1859:209–21.

    Article  CAS  PubMed  Google Scholar 

  129. Kirby K, Hu J, Hilliker AJ, Phillips JP. RNA interference-mediated silencing of Sod2 in Drosophila leads to early adult-onset mortality and elevated endogenous oxidative stress. Proc Natl Acad Sci U S A. 2002;99:16162–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Kirkwood TB, Austad SN. Why do we age? Nature. 2000;408:233–8.

    Article  CAS  PubMed  Google Scholar 

  131. Koga H, Kaushik S, Cuervo AM. Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res Rev. 2011;10:205–15.

    Article  CAS  PubMed  Google Scholar 

  132. Koh K, Evans JM, Hendricks JC, Sehgal A. A Drosophila model for age-associated changes in sleep: wake cycles. Proc Natl Acad Sci U S A. 2006;103:13843–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705.

    Article  CAS  PubMed  Google Scholar 

  134. Kuno A, Horio Y. Anti-aging drugs. Nihon Rinsho. 2009;67:1384–8.

    PubMed  Google Scholar 

  135. Kurapati R, Passananti HB, Rose MR, Tower J. Increased hsp22 RNA levels in Drosophila lines genetically selected for increased longevity. J Gerontol A Biol Sci Med Sci. 2000;55:B552–9.

    Article  CAS  PubMed  Google Scholar 

  136. Lapointe J, Hekimi S. When a theory of ageing ages badly. Cell Mol Life Sci. 2010;67:1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Larson K, Yan SJ, Tsurumi A, Liu J, Zhou J, Gaur K, Guo D, Eickbush TH, et al. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 2012;8:e1002473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Le Bourg E. Oxidative stress, aging and longevity in Drosophila melanogaster. FEBS Lett. 2001;498:183–6.

    Article  PubMed  Google Scholar 

  139. Lee KS, Lee BS, Semnani S, Avanesian A, Um CY, Jeon HJ, Seong KM, Yu K, et al. Curcumin extends lifespan, improves health span, and modulates the expression of age-associated aging genes in Drosophila melanogaster. Rejuvenation Res. 2010;13:561–70.

    Article  CAS  PubMed  Google Scholar 

  140. Li Y, Liu L, Tollefsbol TO. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J. 2010;24:1442–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Liao PC, Lin HY, Yuh CH, Yu LK, Wang HD. The effect of neuronal expression of heat shock proteins 26 and 27 on lifespan, neurodegeneration, and apoptosis in Drosophila. Biochem Biophys Res Commun. 2008;376:637–41.

    Google Scholar 

  142. Libert S, Chao Y, Chu X, Pletcher SD. Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NFkappaB signaling. Aging Cell. 2006;5:533–43.

    Article  CAS  PubMed  Google Scholar 

  143. Lin YJ, Seroude L, Benzer S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science. 1998;282:943–6.

    Article  CAS  PubMed  Google Scholar 

  144. Lin WS, Chen JY, Wang JC, Chen LY, Lin CH, Hsieh TR, Wang MF, Fu TF, et al. The anti-aging effects of Ludwigia octovalvis on Drosophila melanogaster and SAMP8 mice. Age. 2014;36:689–703.

    Article  PubMed  Google Scholar 

  145. Linford NJ, Bilgir C, Ro J, Pletcher SD. Measurement of lifespan in Drosophila melanogaster. J Vis Exp. 2013;71(71):pii 50068.

    Google Scholar 

  146. Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, et al. Genomic instability in laminopathy-based premature aging. Nat Med. 2005;11:780–5.

    Article  CAS  PubMed  Google Scholar 

  147. Liu GH, Suzuki K, Qu J, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, et al. Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell. 2011;8:688–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Loeb J, Northrop JH. Is there a temperature coefficient for the duration of life? Proc Natl Acad Sci U S A. 1916;2:456–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Loeb J, Northrop JH. On the influence of food and temperature upon the duration of life. J Biol Chem. 1917;32:103–21.

    Article  CAS  Google Scholar 

  150. Lopez T, Schriner SE, Okoro M, Lu D, Chiang BT, Huey J, Jafari M. Green tea polyphenols extend the lifespan of male Drosophila melanogaster while impairing reproductive fitness. J Med Food. 2014;17:1314–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–94.

    Article  CAS  PubMed  Google Scholar 

  153. Luckinbill L, Clare M. Selection for lifespan in Drosophila melanogaster. Heredity. 1985;55:9–18.

    Article  PubMed  Google Scholar 

  154. Luckinbill L, Arking R, Clare MJ, Cirocco WC, Buck S. Selection for delayed senescence in Drosophila melanogaster. Evolution. 1984;38:996–1003.

    Article  PubMed  Google Scholar 

  155. Luong N, Davies CR, Wessells RJ, Graham SM, King MT, Veech R, Bodmer R, Oldham SM. Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity. Cell Metab. 2006;4:133–42.

    Article  CAS  PubMed  Google Scholar 

  156. Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, Zhang J, Zhang N, Liang S, et al. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 2010;20:332–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Mair W, Goymer P, Pletcher SD, Partridge L. Demography of dietary restriction and death in Drosophila. Science. 2003;301:1731–3.

    Article  CAS  PubMed  Google Scholar 

  158. Mair W, Piper MD, Partridge L. Calories do not explain extension of lifespan by dietary restriction in Drosophila. PLoS Biol. 2005;7:e223.

    Article  CAS  Google Scholar 

  159. Marino G, Ugalde AP, Fernandez AF, Osorio FG, Fueyo A, Freije JM, Lopez-Otin C. Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function. Proc Natl Acad Sci U S A. 2010;107:16268–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA. DNA damage, DNA repair, aging, and neurodegeneration. Cold Spring Harb Perspect Med. 2015;5:a025130.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. McCarroll SA, Murphy CT, Zou S, Pletcher SD, Chin CS, Jan YN, Kenyon C, Bargmann CI, et al. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet. 2004;36:197–204.

    Article  CAS  PubMed  Google Scholar 

  162. McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of lifespan and upon the ultimate body size. 1935 Nutrition. 1989;5:155–71.

    CAS  PubMed  Google Scholar 

  163. McCord JM, Fridovich I. Superoxide dismutase. An enzymatic function for erythrocuperin (hemocuperin). J Biol Chem. 1969;244:6049–605.

    Article  CAS  PubMed  Google Scholar 

  164. McGuire SE, Le PT, Davis RL. The role of Drosophila mushroom body signaling in olfactory memory. Science. 2001;293:1330–3.

    Article  CAS  PubMed  Google Scholar 

  165. McKiernan SH, Colman RJ, Lopez M, Beasley TM, Aiken JM, Anderson RM, Weindruch R. Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle. Exp Gerontol. 2011;46:23–9.

    Article  CAS  PubMed  Google Scholar 

  166. Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci. 2015;16:345–57.

    Article  CAS  PubMed  Google Scholar 

  167. Min KJ, Flatt T, Kulaots I, Tatar M. Counting calories in Drosophila diet restriction. Exp Gerontol. 2007;42:247–51.

    Article  PubMed  Google Scholar 

  168. Min JN, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol. 2008;28:4018–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Minois N. Longevity and aging: beneficial effects of exposure to mild stress. Biogerontology. 2000;1:15–29.

    Article  CAS  PubMed  Google Scholar 

  170. Minois N, Khazaeli AA, Curtsinger JW. Locomotor activity as a function of age and lifespan in Drosophila melanogaster overexpressing hsp70. Exp Gerontol. 2001;36:1137–53.

    Article  CAS  PubMed  Google Scholar 

  171. Missirlis F, Phillips JP, Jackle H. Cooperative action of antioxidant defense systems in Drosophila. Curr Biol. 2001;11:1272–7.

    Article  CAS  PubMed  Google Scholar 

  172. Mitteldorf J. An epigenetic clock controls aging. Biogerontology. 2016;17:257–65.

    Article  CAS  PubMed  Google Scholar 

  173. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self digestion. Nature. 2008;451:1069–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Mockett RJ, Sohal RS, Orr WC. Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. FASEB J. 1999;13:1733–42.

    Article  CAS  PubMed  Google Scholar 

  175. Morimoto RI. Proteotoxic stress and inducible chaperone networks in neurodegenerative 1002 disease and aging. Genes Dev. 2008;22:1427–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Morley JF, Brignull HR, Weyers JJ, Morimoto RI. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2002;99:10417–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Morrow G, Tanguay RM. Heat shock proteins and aging in Drosophila melanogaster. Semin Cell Dev Biol. 2003;14:291–9.

    Article  CAS  PubMed  Google Scholar 

  178. Morrow G, Battistini S, Zhang P, Tanguay RM. Decreased lifespan in the absence of expression of the mitochondrial small heat shock protein Hsp22 in Drosophila. J Biol Chem. 2004a;279:43382–5.

    Article  CAS  PubMed  Google Scholar 

  179. Morrow G, Samson M, Michaud S, Tanguay RM. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J. 2004b;18:598–9.

    Article  CAS  PubMed  Google Scholar 

  180. Morrow G, Heikkila JJ, Tanguay RM. Differences in the chaperone-like activities of the four main small heat shock proteins of Drosophila melanogaster. Cell Stress Chaperones. 2006;11:51–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Mosammaparast N, Shi Y. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem. 2010;79:155–79.

    Article  CAS  PubMed  Google Scholar 

  182. Moskalev AA, Shaposhnikov MV, Plyusnina EN, Zhavoronkov A, Budovsky A, Yanai H, Fraifeld VE. The role of DNA damage and repair in aging through the prism of Koch-like criteria. Ageing Res Rev. 2012;12:661–84.

    Article  PubMed  CAS  Google Scholar 

  183. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, Mottis A, Jo YS, et al. The NAD(+)/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154:430–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005;6:11–22.

    Article  CAS  PubMed  Google Scholar 

  185. Muchowski PJ, Schaffar G, Sittler A, Wanker EE, Hayer-Hartl MK, Hartl FU. Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci U S A. 2000;97:7841–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Murphy MP. How mitochondria produces reactive oxygen species. Biochem J. 2009;417:1–13.

    Article  CAS  PubMed  Google Scholar 

  187. Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, Kravitz SA, Mobarry CM, et al. A whole-genome assembly of Drosophila. Science. 2000;287:2196–204.

    Article  CAS  PubMed  Google Scholar 

  188. Na H, Park J, Pyo J, Jeon H, Kim Y, Arking R, Yoo M. Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway. Mech Aging Dev. 2015;149:8–18.

    Article  CAS  PubMed  Google Scholar 

  189. Nakagawa H, Nuovo GJ, Zervos EE, Martin EW Jr, Salovaara R, Aaltonen LA, de la Chapelle A. Age-related hypermethylation of the 5′ region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development. Cancer Res. 2001;61:6991–5.

    CAS  PubMed  Google Scholar 

  190. Neto CC. Cranberry and its phytochemicals: a review of in vitro anticancer studies. J Nutr. 2007;137:186S–93S.

    Article  CAS  PubMed  Google Scholar 

  191. Niedzwiecki A, Kongpachith AM, Fleming JE. Aging affects expression of 70-kDa heat shock proteins in Drosophila. J Biol Chem. 1991;266:9332–8.

    Article  CAS  PubMed  Google Scholar 

  192. Nielsen MD, Luo X, Biteau B, Syverson K, Jasper H. 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell. 2008;7:688–99.

    Article  CAS  PubMed  Google Scholar 

  193. Oishi K, Shiota M, Sakamoto K, Kasamatsu M, Ishida N. Feeding is not a more potent Zeitgeber than the light-dark cycle in Drosophila. Neuroreport. 2004;15:739–43.

    Article  PubMed  Google Scholar 

  194. Olovnikov AM. Telomeres, telomerase, and aging: origin of the theory. Exp Gerontol. 1996;31:443–8.

    Article  CAS  PubMed  Google Scholar 

  195. Orr WC, Sohal RS. Effects of Cu-Zn superoxide dismutase overexpression on lifespan and 1034 resistance to oxidative stress in transgeneic D. melanogaster. Arch Biochem Biophys. 1993;301:34–40.

    Article  CAS  PubMed  Google Scholar 

  196. Orr WC, Sohal RS. Extension of life-span by overexpression of superoxide dismutase and 1037 catalase in Drosophila melanogaster. Science. 1994;263:1128–30.

    Article  CAS  PubMed  Google Scholar 

  197. Osorio FG, Navarro CL, Cadinanos J, Lopez-Mejia IC, Quiros PM, Bartoli C, Rivera J, Tazi J, et al. Splicing-directed therapy in a new mouse model of human accelerated aging. Sci Transl Med. 2011;3:106ra107.

    Article  PubMed  CAS  Google Scholar 

  198. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010;285:8340–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Palikaras K, Lionaki E, Tavernarakis N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature. 2015;521:525–8.

    Article  CAS  PubMed  Google Scholar 

  200. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.

    Article  CAS  PubMed  Google Scholar 

  201. Pandey UB, Nichols CD. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev. 2011;63:411–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL. Extension of Drosophila lifespan by overexpression of human SOD1 in motor neurons. Nat Genet. 1998;19:171–4.

    Article  CAS  PubMed  Google Scholar 

  203. Partridge L, Piper MD, Mair W. Dietary restriction in Drosophila. Mech Ageing Dev. 2005;126:938–50.

    Article  CAS  PubMed  Google Scholar 

  204. Pearl R, Parker SL. Experimental studies on duration of life I. Introductory discussion of the duration of life in of Drosophila. Am Nat. 1921a;60:481–509.

    Article  Google Scholar 

  205. Pearl R, Parker SL. Experimental studies on duration of life II. Hereditary differences in duration of life in line-bread strains of Drosophila. Am Nat. 1921b;56:174.

    Article  Google Scholar 

  206. Pegoraro G, Kubben N, Wickert U, Göhler H, Hoffmann K, Misteli T. Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol. 2009;11:1261–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Peng C, Zuo Y, Kwan KM, Liang Y, Ma KY, Chan HY, Huang Y, Yu H, et al. Blueberry extract prolongs lifespan of Drosophila melanogaster. Exp Gerontol. 2012;47:170–8.

    Article  CAS  PubMed  Google Scholar 

  208. Pérez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A. Is the oxidative stress theory of aging dead? Biochim Biophys Acta. 2009;1790:1005–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  209. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300:1140–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Pfeiffenberger C, Lear BC, Keegan KP, Allada R. Locomotor activity level monitoring using the Drosophila activity monitoring (DAM) system. Cold Spring Harb Protoc. 2010;2010(11):pdb.prot5518.

    Article  PubMed  Google Scholar 

  211. Phillips JP, Hilliker AJ. Genetic analysis of oxygen defense mechanisms in Drosophila melanogaster. Adv Genet. 1990;28:43–71.

    Article  CAS  PubMed  Google Scholar 

  212. Phillips JP, Campbell SD, Michaud D, Charbonneau M, Hilliker AJ. Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proc Natl Acad Sci U S A. 1989;86:2761–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Piper MD, Partridge L. Dietary restriction in Drosophila: delayed aging or experimental artefact? PLoS Genet. 2007;3:e57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Piper MD, Blanc E, Leitao-Goncalves R, Yang M, He X, Linford NJ, Hoddinott MP, Hopfen C, et al. A holidic medium for Drosophila melanogaster. Nat Methods. 2014;11:100–5.

    Article  CAS  PubMed  Google Scholar 

  215. Pletcher SD, Macdonald SJ, Marguerie R, Certa U, Stearns SC, Goldstein DB, Partridge L. Genomewide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr Biol. 2002;12:712–23.

    Article  CAS  PubMed  Google Scholar 

  216. Poirier L, Seroude L. Genetic approaches to study aging in Drosophila melanogaster. Age. 2005;27:165–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Pollina EA, Brunet A. Epigenetic regulation of aging stem cells. Oncogene. 2011;30:3105–26.

    Article  CAS  PubMed  Google Scholar 

  218. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009;78:959–91.

    Article  CAS  PubMed  Google Scholar 

  219. Ragnauth CD, Warren DT, Liu Y, McNair R, Tajsic T, Figg N, Shroff R, Skepper J, et al. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation. 2010;121:2200–10.

    Article  CAS  PubMed  Google Scholar 

  220. Randow F, Youle RJ. Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe. 2014;15:403–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Reiter LT, Potocki L, Chien S, Gribskov M, Bier E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001;11:1114–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Ritossa F. A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia. 1962;18:571–3.

    Article  CAS  Google Scholar 

  223. Ritossa F. Discovery of the heat shock response. Cell Stress Chaperones. 1996;1:97–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004;101:15998–6003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Rogina B, Reenan RA, Nilsen SP, Helfand SL. Extended life-span conferred by co transporter gene mutations in Drosophila. Science. 2000;290:2137–40.

    Article  CAS  PubMed  Google Scholar 

  226. Rose MR. Evolutionary biology of aging. New York: Oxford University Press; 1991.

    Google Scholar 

  227. Rose M, Charlesworth B. A test of evolutionary theories of senescence. Nature. 1980;287:141–2.

    Article  CAS  PubMed  Google Scholar 

  228. Rose MR, Charlesworth B. Genetics of life history in Drosophila melanogaster. II. Exploratory selection experiments. Genetics. 1981;97:187–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Rose MR, Vu LN, Park SU, Graves JL Jr. Selection on stress resistance increases longevity in Drosophila melanogaster. Exp Gerontol. 1992;27:241–50.

    Article  CAS  PubMed  Google Scholar 

  230. Rudolph KL, Chang S, Lee HW, Blasco M, Gottlieb GJ, Greider C, DePinho RA. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. 1999;96:701–12.

    Article  CAS  PubMed  Google Scholar 

  231. Ryder E, Ashburner M, Bautista-Llacer R, Drummond J, Webster J, Johnson G, Morley T, Chan YS, et al. The DrosDel deletion collection: a Drosophila genomewide chromosomal deficiency resource. Genetics. 2007;177:615–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Sarkar S, Singh MD, Yadav R, Arunkumar KP, Pitman GW. Heat shock proteins: molecules with assorted functions. Front Biol. 2011;6:312–27.

    Article  CAS  Google Scholar 

  233. Scaffidi P, Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol. 2008;10:452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Schriner SE, Kuramada S, Lopez TE, Truong S, Pham A, Jafari M. Extension of Drosophila lifespan by cinnamon through a sex-specific dependence on the insulin receptor substrate Chico. Exp Gerontol. 2014;60:220–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Sebastián C, Satterstrom FK, Haigis MC, Mostoslavsky R. From sirtuin biology to human diseases: an update. J Biol Chem. 2012;287:42444–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  236. Seto NO, Hayashi S, Tener GM. Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life-span. Proc Natl Acad Sci U S A. 1990;87:4270–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Shaw P, Ocorr K, Bodmer R, Oldham S. Drosophila aging 2006/2007. Exp Gerontol. 2008;43:5–10.

    Article  CAS  PubMed  Google Scholar 

  238. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997;33:787–91.

    Article  CAS  PubMed  Google Scholar 

  239. Sinclair DA. Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev. 2005;126:987–1002.

    Article  CAS  PubMed  Google Scholar 

  240. Singh MD, Raj K, Sarkar S. Drosophila Myc, a novel modifier suppresses the poly(Q) toxicity by modulating the level of CREB binding protein and histone acetylation. Neurobiol Dis. 2013;63:48–61.

    Article  PubMed  CAS  Google Scholar 

  241. Smith JM. The effect of temperature and egg-laying on the longevity of Drosophila subobscura. J Exp Biol. 1958;35:832–42.

    Article  Google Scholar 

  242. Soh JW, Marowsky N, Nichols TJ, Rahman AM, Miah T, Sarao P, Khasawneh R, Unnikrishnan A, et al. Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila. Exp Gerontol. 2013;48:229–39.

    Article  CAS  PubMed  Google Scholar 

  243. Sohal RS. Oxidative stress hypothesis of aging. Free Radic Biol Med. 2002;33:573–4.

    Article  CAS  PubMed  Google Scholar 

  244. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19:418–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010;143:802–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Soti C, Csermely P. Aging and molecular chaperones. Exp Gerontol. 2003;38:1037–40.

    Article  CAS  PubMed  Google Scholar 

  247. Speakman JR, Mitchell SE. Caloric restriction. Mol Asp Med. 2011;32:159–221.

    Article  CAS  Google Scholar 

  248. Stowers RS, Schwarz TL. A genetic method for generating Drosophila eyes composed exclusively of mitotic clones of a single genotype. Genetics. 1999;152:1631–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. Sun J, Tower J. FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the lifespan of adult Drosophila melanogaster flies. Mol Cell Biol. 1999;19:216–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Sun Y, Yolitz J, Wang C, Spangler E, Zhan M, Zou S. Aging studies in Drosophila melanogaster. Methods Mol Biol. 2013;1048:77–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. Talens RP, Christensen K, Putter H, Willemsen G, Christiansen L, Kremer D, Suchiman HE, Slagboom PE, et al. Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell. 2012;11:694–703.

    Article  CAS  PubMed  Google Scholar 

  252. Tatar M. Reproductive aging in invertebrate genetic models. Ann N Y Acad Sci. 2010;1204:149–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Tatar M, Khazaeli AA, Curtsinger JW. Chaperoning extended life. Nature. 1997;390:30.

    Article  CAS  PubMed  Google Scholar 

  254. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001;292:107–10.

    Article  CAS  PubMed  Google Scholar 

  255. Teixeira-Castro A, Ailion M, Jalles A, Brignull HR, Vilaça JL, Dias N, Rodrigues P, Oliveira JF, et al. Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways. Hum Mol Genet. 2011;20:2996–3009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  256. Testa G, Biasi F, Poli G, Chiarpotto E. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des. 2014;20:2950–77.

    Article  CAS  PubMed  Google Scholar 

  257. Theodosiou NA, Xu T. Use of FLP/FRT system to study Drosophila development. Methods. 1998;14:355–65.

    Article  CAS  PubMed  Google Scholar 

  258. Thompson RF, Atzmon G, Gheorghe C, Liang HQ, Lowes C, Greally JM, Barzilai N. Tissue-specific dysregulation of DNA methylation in aging. Aging Cell. 2010;9:506–18.

    Article  CAS  PubMed  Google Scholar 

  259. Tomas-Loba A, Flores I, Fernandez-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borras C, Matheu A, et al. Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell. 2008;135:609–22.

    Article  CAS  PubMed  Google Scholar 

  260. Tower J. Transgenic methods for increasing Drosophila lifespan. Mech Aging Dev. 2000;118:1–14.

    Article  CAS  PubMed  Google Scholar 

  261. Troen BR. The biology of aging. Mt Sinai J Med. 2003;70:3–22.

    PubMed  Google Scholar 

  262. Turrens JF. Superoxide production by the mitochondrial respiratory chain. Biosci Rep. 1997;17:3–8.

    Article  CAS  PubMed  Google Scholar 

  263. Vaĭserman AM, Koliada AK, Koshel NM, Simonenko AV, Pasiukova EG. Effect of the histone deacetylase inhibitor sodium butyrate on the viability and lifespan in Drosophila melanogaster. Adv Gerontol. 2012;25:126–31.

    PubMed  Google Scholar 

  264. Varela I, Cadinanos J, Pendas AM, Gutierrez-Fernandez A, Folgueras AR, Sanchez LM, Zhou Z, Rodriguez FJ, et al. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature. 2005;437:564–8.

    Article  CAS  PubMed  Google Scholar 

  265. Voellmy R. On mechanisms that control heat shock transcription factor activity in metazoan cells. Cell Stress Chaperones. 2004;9:122–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  266. Walker DW, Benzer S. Mitochondrial “swirls” induced by oxygen stress and in the Drosophila mutant hyperswirl. Proc Natl Acad Sci U S A. 2004;101:10290–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Walker GA, Lithgow GJ. Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell. 2003;2:131–9.

    Article  CAS  PubMed  Google Scholar 

  268. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Wallace DC. Mitochondrial DNA variation in human radiation and disease. Cell. 2015;163:33–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  270. Wang MC, Bohmann D, Jasper H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell. 2003;5:811–6.

    Article  CAS  PubMed  Google Scholar 

  271. Wang MC, Bohmann D, Jasper H. JNK extends lifespan and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell. 2005;121:115–25.

    Article  CAS  PubMed  Google Scholar 

  272. Wang C, Yolitz J, Alberico T, Laslo M, Sun Y, Wheeler CT, Sun X, Zou S. Cranberry interacts with dietary macronutrients to promote healthy aging in Drosophila. J Gerontol A Biol Sci. 2014a;69:945–54.

    Article  CAS  Google Scholar 

  273. Wang L, Karpac J, Jasper H. Promoting longevity by maintaining metabolic and proliferative homeostasis. J Exp Biol. 2014b;217:109–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Webb AE, Brunet A. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci. 2014;39:159–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Weiss EP, Racette SB, Villareal DT, Fontana L, Steger-May K, Schechtman KB, Klein S, Holloszy JO. Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am J Clin Nutr. 2006;84:1033–42.

    Article  CAS  PubMed  Google Scholar 

  276. Wiegant FA, Surinova S, Ytsma E, Langelaar-Makkinje M, Wikman G, Post JA. Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology. 2009;10:27–42.

    Article  CAS  PubMed  Google Scholar 

  277. Wolf FW, Heberlein U. Invertebrate models of drug abuse. J Neurobiol. 2003;54:161–78.

    Article  CAS  PubMed  Google Scholar 

  278. Wong R, Piper MD, Wertheim B, Partridge L. Quantification of food intake in Drosophila. PLoS One. 2009;4:e6063.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  279. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686–9.

    Article  CAS  PubMed  Google Scholar 

  280. Worman HJ. Nuclear lamins and laminopathies. J Pathol. 2012;226:316–25.

    Article  CAS  PubMed  Google Scholar 

  281. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–24.

    Article  CAS  PubMed  Google Scholar 

  282. Xu T, Rubin GM. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development. 1993;117:1223–37.

    Article  CAS  PubMed  Google Scholar 

  283. Yadav R, Kundu S, Sarkar S. Drosophila glob1 expresses dynamically and is required for development and oxidative stress response. Genesis. 2015;53:719–37.

    Article  CAS  PubMed  Google Scholar 

  284. Yan L, Gao S, Ho D, Park M, Ge H, Wang C, Tian Y, Lai L, et al. Calorie restriction can reverse, as well as prevent, aging cardiomyopathy. Age (Dordr). 2013;35:2177–82.

    Article  Google Scholar 

  285. Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science. 2012;337:1062–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  286. Yu BP. Approaches to anti-aging intervention: the promises and the uncertainties. Mech Ageing Dev. 1999;111:73–87.

    Article  CAS  PubMed  Google Scholar 

  287. Zeitlinger J, Bohmann D. Thorax closure in Drosophila: involvement of Fos and the JNK pathway. Development. 1999;126:3947–56.

    Article  CAS  PubMed  Google Scholar 

  288. Zhao Y, Sun H, Lu J, Li X, Chen X, Tao D, Huang W, Huang B. Lifespan extension and elevated hsp gene expression in Drosophila caused by histone deacetylase inhibitors. J Exp Biol. 2005;208:697–705.

    Article  CAS  PubMed  Google Scholar 

  289. Zhu M, Hu J, Perez E, Phillips D, Kim W, Ghaedian R, Napora JK, Zou S. Effects of long-term cranberry supplementation on endocrine pancreas in aging rats. J Gerontol A Biol Sci Med Sci. 2011;66:1139–51.

    Article  PubMed  CAS  Google Scholar 

  290. Zou S, Meadows S, Sharp L, Jan LY, Jan YN. Genome-wide study of aging and oxidative stress response in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2000;97:13726–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  291. Zou S, Sinclair J, Wilson MA, Carey JR, Liedo P, Oropeza A, Kalra A, de Cabo R, et al. Comparative approaches to facilitate the discovery of prolongevity interventions: effects of tocopherols on lifespan of three invertebrate species. Mech Ageing Dev. 2007;128:222–6.

    Article  CAS  PubMed  Google Scholar 

  292. Zwaan B, Bijlsma R, Hoekstra RE. Direct selection on life-span in Drosophila melanogaster. Evolution. 1995;49:649–59.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Research programs in the laboratory have been supported by grants from the Department of Science and Technology (DST), Department of Biotechnology (DBT), Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi, and DU/DST-PURSE scheme to SS. Nisha, KR, Pragati, ST, and SIC are supported by DBT-SRF, UGC-SRF, CSIR-JRF, UGC-JRF, and UGC-SRF fellowships, respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Surajit Sarkar .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nisha, Raj, K., Pragati, Tandon, S., Chanu, S.I., Sarkar, S. (2020). Aging: Reading, Reasoning, and Resolving Using Drosophila as a Model System. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9005-1_14

Download citation

Publish with us

Policies and ethics