Cellular and Molecular Life Sciences

, Volume 75, Issue 1, pp 93–101 | Cite as

Role of gut microbiota in aging-related health decline: insights from invertebrate models

  • Rebecca I. ClarkEmail author
  • David W. WalkerEmail author
Multi-author review


Studies in mammals, including humans, have reported age-related changes in microbiota dynamics. A major challenge, however, is to dissect the cause and effect relationships involved. Invertebrate model organisms such as the fruit fly Drosophila and the nematode Caenorhabditis elegans have been invaluable in studies of the biological mechanisms of aging. Indeed, studies in flies and worms have resulted in the identification of a number of interventions that can slow aging and prolong life span. In this review, we discuss recent work using invertebrate models to provide insight into the interplay between microbiota dynamics, intestinal homeostasis during aging and life span determination. An emerging theme from these studies is that the microbiota contributes to cellular and physiological changes in the aging intestine and, in some cases, age-related shifts in microbiota dynamics can drive health decline in aged animals.


Intestinal barrier Microbiome Dysbiosis Longevity Mortality 



We apologize to our colleagues whose work we were unable to discuss due to space limitations. D.W.W is supported by the National Institute on Aging (R01AG037514, R01AG049157, and R01AG040288). This review was written while D.W.W was a Julie Martin Mid‐Career Awardee in Aging Research supported by the Ellison Medical Foundation and AFAR.


  1. 1.
    Gems D, Partridge L (2013) Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol 75:621–644. doi: 10.1146/annurev-physiol-030212-183712 CrossRefPubMedGoogle Scholar
  2. 2.
    Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512. doi: 10.1038/nature08980 CrossRefPubMedGoogle Scholar
  3. 3.
    Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, Curiel TJ, de Cabo R, Franceschi C, Gems D, Ingram DK, Johnson TE, Kennedy BK, Kenyon C, Klein S, Kopchick JJ, Lepperdinger G, Madeo F, Mirisola MG, Mitchell JR, Passarino G, Rudolph KL, Sedivy JM, Shadel GS, Sinclair DA, Spindler SR, Suh Y, Vijg J, Vinciguerra M, Fontana L (2015) Interventions to slow aging in humans: are we ready? Aging Cell 14(4):497–510. doi: 10.1111/acel.12338 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350(6265):1191–1193. doi: 10.1126/science.aad3267 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328(5976):321–326. doi: 10.1126/science.1172539 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Libina N, Berman JR, Kenyon C (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115(4):489–502CrossRefPubMedGoogle Scholar
  7. 7.
    Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144(1):79–91. doi: 10.1016/j.cell.2010.12.016 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Biteau B, Karpac J, Supoyo S, Degennaro M, Lehmann R, Jasper H (2010) Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet 6(10):e1001159. doi: 10.1371/journal.pgen.1001159 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Guo L, Karpac J, Tran SL, Jasper H (2014) PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 156(1–2):109–122. doi: 10.1016/j.cell.2013.12.018 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hur JH, Bahadorani S, Graniel J, Koehler CL, Ulgherait M, Rera M, Jones DL, Walker DW (2013) Increased longevity mediated by yeast NDI1 expression in Drosophila intestinal stem and progenitor cells. Aging (Albany NY) 5(9):662–681CrossRefGoogle Scholar
  11. 11.
    Rera M, Azizi MJ, Walker DW (2013) Organ-specific mediation of lifespan extension: more than a gut feeling? Ageing Res Rev 12(1):436–444. doi: 10.1016/j.arr.2012.05.003 CrossRefPubMedGoogle Scholar
  12. 12.
    Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M, Hur JH, Ansari WS, Lo T Jr, Jones DL, Walker DW (2011) Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab 14(5):623–634. doi: 10.1016/j.cmet.2011.09.013 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ulgherait M, Rana A, Rera M, Graniel J, Walker DW (2014) AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep 8(6):1767–1780. doi: 10.1016/j.celrep.2014.08.006 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li H, Qi Y, Jasper H (2016) Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan. Cell Host Microbe 19(2):240–253. doi: 10.1016/j.chom.2016.01.008 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Jasper H (2015) Exploring the physiology and pathology of aging in the intestine of Drosophila melanogaster. Invertebr Reprod Dev 59(sup1):51–58. doi: 10.1080/07924259.2014.963713 CrossRefPubMedGoogle Scholar
  16. 16.
    Zoetendal EG, Akkermans ADL, De Vos WM (1998) Temperature gradient gel electrophoresis analysis of 16S rRNA from human fecal samples reveals stable and host-specific communities of active bacteria. Appl Environ Microbiol 64(10):3854–3859PubMedPubMedCentralGoogle Scholar
  17. 17.
    Rajilić-Stojanović M, Heilig HGHJ, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM (2009) Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol 11(7):1736–1751. doi: 10.1111/j.1462-2920.2009.01900.x CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Curtis M (2016) An introduction to microbial dysbiosis. In: Henderson B, Nibali L (eds) The human microbiota and chronic disease. Dysbiosis as a cause of human pathology. Wiley, Blackwell Publishing (Holdings) Ltd, Hoboken, New Jersey, United StatesGoogle Scholar
  19. 19.
    Clemente JC, Ursell LK, Parfrey LW, Knight R (2012) The impact of the gut microbiota on human health: an integrative view. Cell 148(6):1258–1270. doi: 10.1016/j.cell.2012.01.035 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    O’Toole PW, Jeffery IB (2015) Gut microbiota and aging. Science 350(6265):1214–1215. doi: 10.1126/science.aac8469 CrossRefPubMedGoogle Scholar
  21. 21.
    Belizário JE, Napolitano M (2015) Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol. doi: 10.3389/fmicb.2015.01050 PubMedPubMedCentralGoogle Scholar
  22. 22.
    Consortium TIHiRN (2014) The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe 16(3):276–289. doi: 10.1016/j.chom.2014.08.014 CrossRefGoogle Scholar
  23. 23.
    McGhee JD (2007) The C. elegans intestine. In: Community TCer (ed) WormBook. doi: 10.1895/wormbook.1.133.1
  24. 24.
    Buchon N, Osman D, David FP, Fang HY, Boquete JP, Deplancke B, Lemaitre B (2013) Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep 3(5):1725–1738. doi: 10.1016/j.celrep.2013.04.001 CrossRefPubMedGoogle Scholar
  25. 25.
    Lemaitre B, Miguel-Aliaga I (2013) The digestive tract of Drosophila melanogaster. Annu Rev Genet 47:377–404. doi: 10.1146/annurev-genet-111212-133343 CrossRefPubMedGoogle Scholar
  26. 26.
    Tissenbaum HA (2015) Using C. elegans for aging research. Invertebr Reprod Dev 59(sup1):59–63. doi: 10.1080/07924259.2014.940470 CrossRefPubMedGoogle Scholar
  27. 27.
    Melov S (2016) Geroscience approaches to increase healthspan and slow aging. F1000Res. doi: 10.12688/f1000research.7583.1 PubMedPubMedCentralGoogle Scholar
  28. 28.
    Consortium THMP (2012) Structure, function and diversity of the healthy human microbiome. Nature 486(7402):207–214. doi: 10.1038/nature11234 CrossRefGoogle Scholar
  29. 29.
    Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto J-M, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J, Weissenbach J, Ehrlich SD, Bork P (2011) Enterotypes of the human gut microbiome. Nature 473(7346):174–180. doi: 10.1038/nature09944 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A, McDonald D, Knight R (2014) Rethinking “Enterotypes”. Cell Host Microbe 16(4):433–437. doi: 10.1016/j.chom.2014.09.013 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Derrien M, Vlieg JETvH (2015) Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol 23(6):354–366. doi: 10.1016/j.tim.2015.03.002 CrossRefPubMedGoogle Scholar
  32. 32.
    Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, Weerd Hd, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, Dv Sinderen, O’Connor M, Harnedy N, O’Connor K, Henry C, O’Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O’Toole PW (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci 108(Supplement 1):4586–4591. doi: 10.1073/pnas.1000097107 CrossRefPubMedGoogle Scholar
  33. 33.
    Mariat D, Firmesse O, Levenez F, Guimarăes VD, Sokol H, Doré J, Corthier G, Furet JP (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123. doi: 10.1186/1471-2180-9-123 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. doi: 10.1371/journal.pone.0010667 Google Scholar
  35. 35.
    Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, Fitzgerald GF, Deane J, O’Connor M, Harnedy N, O’Connor K, O’Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O’Toole PW (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184. doi: 10.1038/nature11319 CrossRefPubMedGoogle Scholar
  36. 36.
    Jeffery IB, Lynch DB, O’Toole PW (2016) Composition and temporal stability of the gut microbiota in older persons. ISME J 10(1):170–182. doi: 10.1038/ismej.2015.88 CrossRefPubMedGoogle Scholar
  37. 37.
    van Tongeren SP, Slaets JPJ, Harmsen HJM, Welling GW (2005) Fecal microbiota composition and frailty. Appl Environ Microbiol 71(10):6438–6442. doi: 10.1128/AEM.71.10.6438-6442 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Jackson MA, Jeffery IB, Beaumont M, Bell JT, Clark AG, Ley RE, O’Toole PW, Spector TD, Steves CJ (2016) Signatures of early frailty in the gut microbiota. Genome Med. doi: 10.1186/s13073-016-0262-7 Google Scholar
  39. 39.
    Langille MGI, Meehan CJ, Koenig JE, Dhanani AS, Rose RA, Howlett SE, Beiko RG (2014) Microbial shifts in the aging mouse gut. Microbiome. doi: 10.1186/s40168-014-0050-9 PubMedPubMedCentralGoogle Scholar
  40. 40.
    Samuel BS, Rowedder H, Braendle C, Félix M-A, Ruvkun G (2016) Caenorhabditis elegans responses to bacteria from its natural habitats. Proc Natl Acad Sci 113(27):E3941–E3949. doi: 10.1073/pnas.1607183113 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Dirksen P, Marsh SA, Braker I, Heitland N, Wagner S, Nakad R, Mader S, Petersen C, Kowallik V, Rosenstiel P, Félix M-A, Schulenburg H (2016) The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model. BMC Biol. doi: 10.1186/s12915-016-0258-1 PubMedPubMedCentralGoogle Scholar
  42. 42.
    Wong ACN, Chaston JM, Douglas AE (2013) The inconstant gut microbiota of Drosophila species revealed by 16S rRNA gene analysis. ISME J 7(10):1922–1932. doi: 10.1038/ismej.2013.86 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Chandler JA, Morgan Lang J, Bhatnagar S, Eisen JA, Kopp A (2011) Bacterial communities of diverse Drosophila species: ecological context of a host–microbe model system. PLoS Genet. doi: 10.1371/journal.pgen.1002272 PubMedPubMedCentralGoogle Scholar
  44. 44.
    Corby-Harris V, Pontaroli AC, Shimkets LJ, Bennetzen JL, Habel KE, Promislow DEL (2007) Geographical distribution and diversity of bacteria associated with natural populations of Drosophila melanogaster. Appl Environ Microbiol 73(11):3470–3479. doi: 10.1128/AEM.02120-06 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Cox CR, Gilmore MS (2007) Native microbial colonization of Drosophila melanogaster and its use as a model of Enterococcus faecalis pathogenesis. Infect Immun 75(4):1565–1576. doi: 10.1128/IAI.01496-06 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Wong ACN, Luo Y, Jing X, Franzenburg S, Bost A, Douglas AE (2015) The host as the driver of the microbiota in the gut and external environment of Drosophila melanogaster. Appl Environ Microbiol 81(18):6232–6240. doi: 10.1128/AEM.01442-15 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Storelli G, Defaye A, Erkosar B, Hols P, Royet J, Leulier F (2011) Lactobacillus plantarum promotes drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab 14(3):403–414. doi: 10.1016/j.cmet.2011.07.012 CrossRefPubMedGoogle Scholar
  48. 48.
    Shin SC, Kim S-H, You H, Kim B, Kim AC, Lee K-A, Yoon J-H, Ryu J-H, Lee W-J (2011) Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334(6056):670–674. doi: 10.1126/science.1212782 CrossRefPubMedGoogle Scholar
  49. 49.
    Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161(3):1101–1112PubMedPubMedCentralGoogle Scholar
  50. 50.
    Portal-Celhay C, Bradley ER, Blaser MJ (2012) Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans. BMC Microbiol 12:49. doi: 10.1186/1471-2180-12-49 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Gomez F, Monsalve GC, Tse V, Saiki R, Weng E, Lee L, Srinivasan C, Frand AR, Clarke CF (2012) Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli. BMC Microbiol 12:300. doi: 10.1186/1471-2180-12-300 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Erkosar B, Storelli G, Defaye A, Leulier F (2013) Host-intestinal microbiota mutualism: “learning on the fly”. Cell Host Microbe 13(1):8–14. doi: 10.1016/j.chom.2012.12.004 CrossRefPubMedGoogle Scholar
  53. 53.
    Broderick NA, Lemaitre B (2012) Gut-associated microbes of Drosophila melanogaster. Gut Microbes 3(4):307–321. doi: 10.4161/gmic.19896 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Clark RI, Salazar A, Yamada R, Fitz-Gibbon S, Morselli M, Alcaraz J, Rana A, Rera M, Pellegrini M, Ja WW, Walker DW (2015) Distinct shifts in microbiota composition during drosophila aging impair intestinal function and drive mortality. Cell Rep 12(10):1656–1667. doi: 10.1016/j.celrep.2015.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Broderick NA, Buchon N, Lemaitre B (2014) Microbiota-induced changes in Drosophila melanogaster host gene expression and gut morphology. MBio 5(3):e01117–e01214. doi: 10.1128/mBio.01117-14 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Buchon N, Broderick NA, Chakrabarti S, Lemaitre B (2009) Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23(19):2333–2344. doi: 10.1101/gad.1827009 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Ren C, Webster P, Finkel SE, Tower J (2007) Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab 6(2):144–152. doi: 10.1016/j.cmet.2007.06.006 CrossRefPubMedGoogle Scholar
  58. 58.
    McGee MD, Weber D, Day N, Vitelli C, Crippen D, Herndon LA, Hall DH, Melov S (2011) Loss of intestinal nuclei and intestinal integrity in aging C. elegans. Aging Cell 10(4):699–710. doi: 10.1111/j.1474-9726.2011.00713.x CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3(4):442–455. doi: 10.1016/j.stem.2008.07.024 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Choi N-H, Kim J-G, Yang D-J, Kim Y-S, Yoo M-A (2008) Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell 7(3):318–334. doi: 10.1111/j.1474-9726.2008.00380.x CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Park J-S, Kim Y-S, Yoo M-A (2009) The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila. Aging 1(7):637–651. doi: 10.18632/aging.100054 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Li H, Jasper H (2016) Gastrointestinal stem cells in health and disease: from flies to humans. Dis Models Mech 9(5):487–499. doi: 10.1242/dmm.024232 CrossRefGoogle Scholar
  63. 63.
    Chen H, Zheng X, Zheng Y (2014) Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia. Cell 159(4):829–843. doi: 10.1016/j.cell.2014.10.028 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Petkau K, Parsons BD, Duggal A, Foley E (2014) A deregulated intestinal cell cycle program disrupts tissue homeostasis without affecting longevity in Drosophila. J Biol Chem 289(41):28719–28729. doi: 10.1074/jbc.M114.578708 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Rera M, Clark RI, Walker DW (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci USA 109(52):21528–21533. doi: 10.1073/pnas.1215849110 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Dambroise E, Monnier L, Ruisheng L, Aguilaniu H, Joly JS, Tricoire H, Rera M (2016) Two phases of aging separated by the Smurf transition as a public path to death. Sci Rep. doi: 10.1038/srep23523 PubMedPubMedCentralGoogle Scholar
  67. 67.
    Gelino S, Chang JT, Kumsta C, She X, Davis A, Nguyen C, Panowski S, Hansen M (2016) Intestinal autophagy improves healthspan and longevity in C. elegans during dietary restriction. PLoS Genet. doi: 10.1371/journal.pgen.1006135 Google Scholar
  68. 68.
    Kavanagh K, Brown RN, Davis AT, Uberseder B, Floyd E, Pfisterer B, Shively CA (2016) Microbial translocation and skeletal muscle in young and old vervet monkeys. Age (Dordrecht, Netherlands) 38(3):58. doi: 10.1007/s11357-016-9924-z CrossRefGoogle Scholar
  69. 69.
    Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP, Schertzer JD, Larché MJ, Davidson DJ, Verdú EF, Surette MG, Bowdish DME (2017) Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21(4):455.e454–466.e454. doi: 10.1016/j.chom.2017.03.002 CrossRefGoogle Scholar
  70. 70.
    Karpac J, Biteau B, Jasper H (2013) Misregulation of an adaptive metabolic response contributes to the age-related disruption of lipid homeostasis in Drosophila. Cell reports. doi: 10.1016/j.celrep.2013.08.004 PubMedPubMedCentralGoogle Scholar
  71. 71.
    Houthoofd K, Braeckman BP, Lenaerts I, Brys K, De Vreese A, Van Eygen S, Vanfleteren JR (2002) Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Exp Gerontol 37(12):1371–1378CrossRefPubMedGoogle Scholar
  72. 72.
    Brummel T, Ching A, Seroude L, Simon AF, Benzer S (2004) Drosophila lifespan enhancement by exogenous bacteria. Proc Natl Acad Sci USA 101(35):12974–12979. doi: 10.1073/pnas.0405207101 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Yamada R, Deshpande SA, Bruce KD, Mak EM, Ja WW (2015) Microbes promote amino acid harvest to rescue undernutrition in Drosophila. Cell Rep. doi: 10.1016/j.celrep.2015.01.018 Google Scholar
  74. 74.
    Gems D, Riddle DL (2000) Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154(4):1597–1610PubMedPubMedCentralGoogle Scholar
  75. 75.
    Larsen PL, Clarke CF (2002) Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science 295(5552):120–123. doi: 10.1126/science.1064653 CrossRefPubMedGoogle Scholar
  76. 76.
    Saiki R, Lunceford AL, Bixler T, Dang P, Lee W, Furukawa S, Larsen PL, Clarke CF (2008) Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q. Aging Cell 7(3):291–304. doi: 10.1111/j.1474-9726.2008.00378.x CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Virk B, Jia J, Maynard CA, Raimundo A, Lefebvre J, Richards SA, Chetina N, Liang Y, Helliwell N, Cipinska M, Weinkove D (2016) Folate acts in E. coli to accelerate C. elegans aging independently of bacterial biosynthesis. Cell Rep 14(7):1611–1620. doi: 10.1016/j.celrep.2016.01.051 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Sanchez-Blanco A, Kim SK (2011) Variable pathogenicity determines individual lifespan in Caenorhabditis elegans. PLoS Genet 7(4):e1002047. doi: 10.1371/journal.pgen.1002047 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Khanna A, Kumar J, Vargas MA, Barrett L, Katewa S, Li P, McCloskey T, Sharma A, Naude N, Nelson C, Brem R, Killilea DW, Mooney SD, Gill M, Kapahi P (2016) A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans. Sci Rep 6:38764. doi: 10.1038/srep38764 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Virk B, Correia G, Dixon DP, Feyst I, Jia J, Oberleitner N, Briggs Z, Hodge E, Edwards R, Ward J, Gems D, Weinkove D (2012) Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model. BMC Biol 10:67. doi: 10.1186/1741-7007-10-67 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Heintz C, Mair W (2014) You are what you host: microbiome modulation of the aging process. Cell 156(3):408–411. doi: 10.1016/j.cell.2014.01.025 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Gusarov I, Gautier L, Smolentseva O, Shamovsky I, Eremina S, Mironov A, Nudler E (2013) Bacterial nitric oxide extends the lifespan of C. elegans. Cell 152(4):818–830. doi: 10.1016/j.cell.2012.12.043 CrossRefPubMedGoogle Scholar
  83. 83.
    Liu H, Wang X, Wang HD, Wu J, Ren J, Meng L, Wu Q, Dong H, Wu J, Kao TY, Ge Q, Wu ZX, Yuh CH, Shan G (2012) Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans. Nat Commun 3:1073. doi: 10.1038/ncomms2071 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Burkewitz K, Zhang Y, Mair WB (2014) AMPK at the nexus of energetics and aging. Cell Metab 20(1):10–25. doi: 10.1016/j.cmet.2014.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Gelino S, Hansen M (2012) Autophagy—an emerging anti-aging mechanism. J Clin Exp Pathol (Suppl 4):006Google Scholar
  86. 86.
    Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11(6):453–465. doi: 10.1016/j.cmet.2010.05.001 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G (2009) Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev 23(4):496–511. doi: 10.1101/gad.1775409 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Pang S, Curran SP (2014) Adaptive capacity to bacterial diet modulates aging in C. elegans. Cell Metab 19(2):221–231. doi: 10.1016/j.cmet.2013.12.005 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cocheme HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D (2013) Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153(1):228–239. doi: 10.1016/j.cell.2013.02.035 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Craven M, Egan CF, Dowd SE, McDonough SP, Dogan B, Denkers EY, Bowman D, Scherl EJ, Simpson KW (2012) Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn’s disease. PLoS One 7(7):e41594. doi: 10.1371/journal.pone.0041594 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Dantoft W, Lundin D, Esfahani S, Engstrom Y (2016) The POU/Oct transcription factor Pdm1/nub Is necessary for a beneficial gut microbiota and normal lifespan of Drosophila. J Innate Immun 8(4):412–426. doi: 10.1159/000446368 CrossRefPubMedGoogle Scholar
  92. 92.
    Lewis James D, Chen Eric Z, Baldassano Robert N, Otley Anthony R, Griffiths Anne M, Lee D, Bittinger K, Bailey A, Friedman Elliot S, Hoffmann C, Albenberg L, Sinha R, Compher C, Gilroy E, Nessel L, Grant A, Chehoud C, Li H, Wu Gary D, Bushman Frederic D (2015) Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe 18(4):489–500. doi: 10.1016/j.chom.2015.09.008 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of BiosciencesDurham UniversityDurhamUK
  2. 2.Department of Integrative Biology and PhysiologyUniversity of California, Los AngelesLos AngelesUSA
  3. 3.Molecular Biology InstituteUniversity of California, Los AngelesLos AngelesUSA

Personalised recommendations