1932

Abstract

Sensory neurons provide organisms with data about the world in which they live, for the purpose of successfully exploiting their environment. The consequences of sensory perception are not simply limited to decision-making behaviors; evidence suggests that sensory perception directly influences physiology and aging, a phenomenon that has been observed in animals across taxa. Therefore, understanding the neural mechanisms by which sensory input influences aging may uncover novel therapeutic targets for aging-related physiologies. In this review, we examine different perceptive experiences that have been most clearly linked to aging or age-related disease: food perception, social perception, time perception, and threat perception. For each, the sensory cues, receptors, and/or pathways that influence aging as well as the individual or groups of neurons involved, if known, are discussed. We conclude with general thoughts about the potential impact of this line of research on human health and aging.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021119-034440
2020-02-10
2024-04-21
Loading full text...

Full text loading...

/deliver/fulltext/physiol/82/1/annurev-physiol-021119-034440.html?itemId=/content/journals/10.1146/annurev-physiol-021119-034440&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    McCay CM, Crowell MF, Maynard LA 1935. The effect of retarded growth upon the length of life span and upon the ultimate body size: one figure. J. Nutr. 10:63–79
    [Google Scholar]
  2. 2. 
    Pearl R, Parker SL. 1922. Experimental studies on the duration of life. II. Hereditary differences in duration of life in line-bred strains of Drosophila. Am. Nat 56:174–87
    [Google Scholar]
  3. 3. 
    Johnson TE, Friedman DB, Fitzpatrick PA, Conley WL 1987. Mutant genes that extend life span. Basic Life Sci 42:91–100
    [Google Scholar]
  4. 4. 
    Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R 1993. A C.elegans mutant that lives twice as long as wild type. Nature 366:461–64
    [Google Scholar]
  5. 5. 
    Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G 2013. The hallmarks of aging. Cell 153:1194–217
    [Google Scholar]
  6. 6. 
    Weindruch R, Walford RL. 1982. Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 215:1415–18
    [Google Scholar]
  7. 7. 
    Ikeno Y, Hubbard GB, Lee S, Cortez LA, Lew CM et al. 2009. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J. Gerontol. A Biol. Sci. Med. Sci. 64:522–29
    [Google Scholar]
  8. 8. 
    Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ et al. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–4
    [Google Scholar]
  9. 9. 
    Apfeld J, Kenyon C. 1999. Regulation of lifespan by sensory perception in Caenorhabditiselegans. Nature 402:804–9
    [Google Scholar]
  10. 10. 
    Alcedo J, Kenyon C. 2004. Regulation of C.elegans longevity by specific gustatory and olfactory neurons. Neuron 41:45–55
    [Google Scholar]
  11. 11. 
    Linford NJ, Kuo TH, Chan TP, Pletcher SD 2011. Sensory perception and aging in model systems: from the outside. Annu. Rev. Cell Dev. Biol. 27:759–85
    [Google Scholar]
  12. 12. 
    Riera CE, Huising MO, Follett P, Leblanc M, Halloran J et al. 2014. TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell 157:1023–36
    [Google Scholar]
  13. 13. 
    Kopec S. 1928. On the influence of intermittent starvation on the longevity of the imaginal stage of Drosophila melanogaster. J. Exp. Biol 5:204–11
    [Google Scholar]
  14. 14. 
    Fontana L, Partridge L, Longo VD 2010. Extending healthy life span—from yeast to humans. Science 328:321–26
    [Google Scholar]
  15. 15. 
    Simpson SJ, Le Couteur DG, Raubenheimer D, Solon-Biet SM, Cooney GJ et al. 2017. Dietary protein, aging and nutritional geometry. Ageing Res. Rev. 39:78–86
    [Google Scholar]
  16. 16. 
    Ro J, Pak G, Malec PA, Lyu Y, Allison DB et al. 2016. Serotonin signaling mediates protein valuation and aging. eLife 5:e16843
    [Google Scholar]
  17. 17. 
    Liu Q, Tabuchi M, Liu S, Kodama L, Horiuchi W et al. 2017. Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger. Science 356:534–39
    [Google Scholar]
  18. 18. 
    Guilherme A, Pedersen DJ, Henchey E, Henriques FS, Danai LV et al. 2017. Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming. Mol. Metab. 6:781–96
    [Google Scholar]
  19. 19. 
    Ostojic I, Boll W, Waterson MJ, Chan T, Chandra R et al. 2014. Positive and negative gustatory inputs affect Drosophila lifespan partly in parallel to dFOXO signaling. PNAS 111:8143–48
    [Google Scholar]
  20. 20. 
    Riera CE, Tsaousidou E, Halloran J, Follett P, Hahn O et al. 2017. The sense of smell impacts metabolic health and obesity. Cell Metab 26:198–211.e5
    [Google Scholar]
  21. 21. 
    Artan M, Jeong DE, Lee D, Kim YI, Son HG et al. 2016. Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides. Genes Dev 30:1047–57
    [Google Scholar]
  22. 22. 
    Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD 2007. Regulation of Drosophila life span by olfaction and food-derived odors. Science 315:1133–37
    [Google Scholar]
  23. 23. 
    Gerofotis CD, Ioannou CS, Nakas CT, Papadopoulos NT 2016. The odor of a plant metabolite affects life history traits in dietary restricted adult olive flies. Sci. Rep. 6:28540
    [Google Scholar]
  24. 24. 
    Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD 2008. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 7:478–90
    [Google Scholar]
  25. 25. 
    Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE et al. 2014. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab 19:418–30
    [Google Scholar]
  26. 26. 
    Schlotterer A, Kukudov G, Bozorgmehr F, Hutter H, Du X et al. 2009. C.elegans as model for the study of high glucose-mediated life span reduction. Diabetes 58:2450–56
    [Google Scholar]
  27. 27. 
    May CE, Vaziri A, Lin YQ, Grushko O, Khabiri M et al. 2019. High dietary sugar reshapes sweet taste to promote feeding behavior in Drosophila melanogaster. Cell Rep 27:1675–85.e7
    [Google Scholar]
  28. 28. 
    Musselman LP, Fink JL, Narzinski K, Ramachandran PV, Hathiramani SS et al. 2011. A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. . Dis. Model. Mech 4:842–49
    [Google Scholar]
  29. 29. 
    Winzell MS, Ahren B. 2004. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53:Suppl. 3S215–19
    [Google Scholar]
  30. 30. 
    Narita T, Weinert BT, Choudhary C 2019. Functions and mechanisms of non-histone protein acetylation. Nat. Rev. Mol. Cell Biol. 20:156–74
    [Google Scholar]
  31. 31. 
    Linford NJ, Ro J, Chung BY, Pletcher SD 2015. Gustatory and metabolic perception of nutrient stress in Drosophila. PNAS 112:2587–92
    [Google Scholar]
  32. 32. 
    Waterson MJ, Chan TP, Pletcher SD 2015. Adaptive physiological response to perceived scarcity as a mechanism of sensory modulation of life span. J. Gerontol. Ser. A 70:1088–91
    [Google Scholar]
  33. 33. 
    Altintas O, Park S, Lee SJ 2016. The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C.elegans and D. melanogaster. BMB Rep 49:81–92
    [Google Scholar]
  34. 34. 
    Gems D, Partridge L. 2013. Genetics of longevity in model organisms: debates and paradigm shifts. Annu. Rev. Physiol. 75:621–44
    [Google Scholar]
  35. 35. 
    Murtaza G, Khan AK, Rashid R, Muneer S, Hasan SMF, Chen J 2017. FOXO transcriptional factors and long-term living. Oxid. Med. Cell. Longev. 2017:3494289
    [Google Scholar]
  36. 36. 
    Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J et al. 2005. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. PNAS 102:3105–10
    [Google Scholar]
  37. 37. 
    Hwangbo DS, Gersham B, Tu M-P, Palmer M, Tatar M 2004. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562–66
    [Google Scholar]
  38. 38. 
    Alic N, Tullet JM, Niccoli T, Broughton S, Hoddinott MP et al. 2014. Cell non-autonomous effects of dFOXO/DAF-16 in aging. Cell Rep 6:608–16
    [Google Scholar]
  39. 39. 
    Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K et al. 2007. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr. Biol 17:1646–56
    [Google Scholar]
  40. 40. 
    Tullet JM. 2015. DAF-16 target identification in C.elegans: past, present and future. Biogerontology 16:221–34
    [Google Scholar]
  41. 41. 
    Johnson DW, Llop JR, Farrell SF, Yuan J, Stolzenburg LR, Samuelson AV 2014. The Caenorhabditiselegans Myc-Mondo/Mad complexes integrate diverse longevity signals. PLOS Genet 10:e1004278
    [Google Scholar]
  42. 42. 
    Mattila J, Havula E, Suominen E, Teesalu M, Surakka I et al. 2015. Mondo-Mlx mediates organismal sugar sensing through the Gli-similar transcription factor Sugarbabe. Cell Rep 13:350–64
    [Google Scholar]
  43. 43. 
    Docherty JEB, Manno JE, McDermott JE, DiAngelo JR 2015. Mio acts in the Drosophila brain to control nutrient storage and feeding. Gene 568:190–95
    [Google Scholar]
  44. 44. 
    Iizuka K, Takeda J, Horikawa Y 2009. Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes. FEBS Lett 583:2882–86
    [Google Scholar]
  45. 45. 
    Fisher FM, Maratos-Flier E. 2016. Understanding the physiology of FGF21. Annu. Rev. Physiol. 78:223–41
    [Google Scholar]
  46. 46. 
    Salminen A, Kaarniranta K, Kauppinen A 2017. Regulation of longevity by FGF21: interaction between energy metabolism and stress responses. Ageing Res. Rev. 37:79–93
    [Google Scholar]
  47. 47. 
    Zhang Y, Xie Y, Berglund ED, Coate KC, He TT et al. 2012. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. eLife 1:e00065
    [Google Scholar]
  48. 48. 
    Jiao Y, Moon SJ, Wang X, Ren Q, Montell C 2008. Gr64f is required in combination with other gustatory receptors for sugar detection in Drosophila.Curr. Biol 18:1797–801
    [Google Scholar]
  49. 49. 
    Murovets VO, Bachmanov AA, Zolotarev VA 2015. Impaired glucose metabolism in mice lacking the Tas1r3 taste receptor gene. PLOS ONE 10:e0130997
    [Google Scholar]
  50. 50. 
    Wauson EM, Zaganjor E, Lee AY, Guerra ML, Ghosh AB et al. 2012. The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Mol. Cell 47:851–62
    [Google Scholar]
  51. 51. 
    Ugrankar R, Theodoropoulos P, Akdemir F, Henne WM, Graff JM 2018. Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11. Commun. Biol. 1:110
    [Google Scholar]
  52. 52. 
    Dus M, Ai M, Suh GSB 2013. Taste-independent nutrient selection is mediated by a brain-specific Na+/solute co-transporter in Drosophila. Nat. Neurosci 16:526–28
    [Google Scholar]
  53. 53. 
    Park JY, Dus M, Kim S, Abu F, Kanai MI et al. 2016. Drosophila SLC5A11 mediates hunger by regulating K+ channel activity. Curr. Biol. 26:1965–74
    [Google Scholar]
  54. 54. 
    De Backer I, Hussain SS, Bloom SR, Gardiner JV 2016. Insights into the role of neuronal glucokinase. Am. J. Physiol. Endocrinol. Metab. 311:E42–55
    [Google Scholar]
  55. 55. 
    Journel M, Chaumontet C, Darcel N, Fromentin G, Tome D 2012. Brain responses to high-protein diets. Adv. Nutr. 3:322–29
    [Google Scholar]
  56. 56. 
    Croset V, Schleyer M, Arguello JR, Gerber B, Benton R 2016. A molecular and neuronal basis for amino acid sensing in the Drosophila larva. Sci. Rep. 6:34871
    [Google Scholar]
  57. 57. 
    Steck K, Walker SJ, Itskov PM, Baltazar C, Moreira JM, Ribeiro C 2018. Internal amino acid state modulates yeast taste neurons to support protein homeostasis in Drosophila. eLife 7:e31625
    [Google Scholar]
  58. 58. 
    Weichhart T. 2018. mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology 64:127–34
    [Google Scholar]
  59. 59. 
    Johnson SC, Rabinovitch PS, Kaeberlein M 2013. mTOR is a key modulator of ageing and age-related disease. Nature 493:338–45
    [Google Scholar]
  60. 60. 
    Kang MJ, Vasudevan D, Kang K, Kim K, Park JE et al. 2017. 4E-BP is a target of the GCN2-ATF4 pathway during Drosophila development and aging. J. Cell Biol. 216:115–29
    [Google Scholar]
  61. 61. 
    Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD et al. 2012. TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab 15:713–24
    [Google Scholar]
  62. 62. 
    Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J et al. 2010. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab 11:35–46
    [Google Scholar]
  63. 63. 
    Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM et al. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–95
    [Google Scholar]
  64. 64. 
    Mazucanti CH, Cabral-Costa JV, Vasconcelos AR, Andreotti DZ, Scavone C, Kawamoto EM 2015. Longevity pathways (mTOR, SIRT, Insulin/IGF-1) as key modulatory targets on aging and neurodegeneration. Curr. Top. Med. Chem. 15:2116–38
    [Google Scholar]
  65. 65. 
    Rousakis A, Vlassis A, Vlanti A, Patera S, Thireos G, Syntichaki P 2013. The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditiselegans. Aging Cell 12:742–51
    [Google Scholar]
  66. 66. 
    Mirzaei H, Suarez JA, Longo VD 2014. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol. Metab. 25:558–66
    [Google Scholar]
  67. 67. 
    Antikainen H, Driscoll M, Haspel G, Dobrowolski R 2017. TOR-mediated regulation of metabolism in aging. Aging Cell 16:1219–33
    [Google Scholar]
  68. 68. 
    Juricic P, Grönke S, Partridge L 2019. Branched-chain amino acids have equivalent effects to other essential amino acids on lifespan and ageing-related traits in Drosophila. J. Gerontol. A Biol. Sci. Med. Sci.
    [Google Scholar]
  69. 69. 
    Mansfeld J, Urban N, Priebe S, Groth M, Frahm C et al. 2015. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing. Nat. Commun. 6:10043
    [Google Scholar]
  70. 70. 
    Purpera MN, Shen L, Taghavi M, Münzberg H, Martin RJ et al. 2012. Impaired branched chain amino acid metabolism alters feeding behavior and increases orexigenic neuropeptide expression in the hypothalamus. J. Endocrinol. 212:85–94
    [Google Scholar]
  71. 71. 
    She P, Reid TM, Bronson SK, Vary TC, Hajnal A et al. 2007. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab 6:181–94
    [Google Scholar]
  72. 72. 
    Neinast MD, Jang C, Hui S, Murashige DS, Chu Q et al. 2018. Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab 29:417–29.e4
    [Google Scholar]
  73. 73. 
    Manière G, Ziegler AB, Geillon F, Featherstone DE, Grosjean Y 2016. Direct sensing of nutrients via a LAT1-like transporter in Drosophila insulin-producing cells. Cell Rep 17:137–48
    [Google Scholar]
  74. 74. 
    Ziegler AB, Manière G, Grosjean Y 2018. JhI-21 plays a role in Drosophila insulin-like peptide release from larval IPCs via leucine transport. Sci. Rep. 8:1908
    [Google Scholar]
  75. 75. 
    Magnan C, Levin BE, Luquet S 2015. Brain lipid sensing and the neural control of energy balance. Mol. Cell. Endocrinol. 418:3–8
    [Google Scholar]
  76. 76. 
    Le Foll C, Levin BE 2016. Fatty acid-induced astrocyte ketone production and the control of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310:R1186–92
    [Google Scholar]
  77. 77. 
    Wortley KE, Anderson KD, Yasenchak J, Murphy A, Valenzuela D et al. 2005. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab 2:421–27
    [Google Scholar]
  78. 78. 
    Füredi N, Mikó A, Gaszner B, Feller D, Rostás I et al. 2018. Activity of the hypothalamic melanocortin system decreases in middle-aged and increases in old rats. J. Gerontol. A 73:438–45
    [Google Scholar]
  79. 79. 
    Sternson SM. 2013. Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77:810–24
    [Google Scholar]
  80. 80. 
    Kaushik S, Rodriguez-Navarro Jose A, Arias E, Kiffin R, Sahu S et al. 2011. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab 14:173–83
    [Google Scholar]
  81. 81. 
    Gendron CM, Kuo TH, Harvanek ZM, Chung BY, Yew JY et al. 2014. Drosophila life span and physiology are modulated by sexual perception and reward. Science 343:544–48
    [Google Scholar]
  82. 82. 
    Itskov PM, Ribeiro C. 2013. The dilemmas of the gourmet fly: the molecular and neuronal mechanisms of feeding and nutrient decision making in Drosophila. Front. Neurosci 7:12
    [Google Scholar]
  83. 83. 
    Kim DH, Shin M, Jung SH, Kim YJ, Jones WD 2017. A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila. PLOS Biol 15:e2000532
    [Google Scholar]
  84. 84. 
    Beshel J, Dubnau J, Zhong Y 2017. A leptin analog locally produced in the brain acts via a conserved neural circuit to modulate obesity-linked behaviors in Drosophila. Cell Metab 25:208–17
    [Google Scholar]
  85. 85. 
    Satoh A, Imai SI, Guarente L 2017. The brain, sirtuins, and ageing. Nat. Rev. Neurosci. 18:362–74
    [Google Scholar]
  86. 86. 
    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 8:1767–80
    [Google Scholar]
  87. 87. 
    Blander G, Guarente L. 2004. The Sir2 family of protein deacetylases. Annu. Rev. Biochem. 73:417–35
    [Google Scholar]
  88. 88. 
    Burkewitz K, Morantte I, Weir HJ, Yeo R, Zhang Y et al. 2015. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell 160:842–55
    [Google Scholar]
  89. 89. 
    Kaeberlein M, McVey M, Guarente L 1999. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomycescerevisiae by two different mechanisms. Genes Dev 13:2570–80
    [Google Scholar]
  90. 90. 
    Tissenbaum HA, Guarente L. 2001. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditiselegans. Nature 410:227–30
    [Google Scholar]
  91. 91. 
    Rogina B, Helfand SL. 2004. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. PNAS 101:15998–6003
    [Google Scholar]
  92. 92. 
    Satoh A, Brace CS, Rensing N, Cliften P, Wozniak DF et al. 2013. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab 18:416–30
    [Google Scholar]
  93. 93. 
    O'Callaghan C, Vassilopoulos A. 2017. Sirtuins at the crossroads of stemness, aging, and cancer. Aging Cell 16:1208–18
    [Google Scholar]
  94. 94. 
    Herskovits AZ, Guarente L. 2014. SIRT1 in neurodevelopment and brain senescence. Neuron 81:471–83
    [Google Scholar]
  95. 95. 
    Watroba M, Dudek I, Skoda M, Stangret A, Rzodkiewicz P, Szukiewicz D 2017. Sirtuins, epigenetics and longevity. Ageing Res. Rev. 40:11–19
    [Google Scholar]
  96. 96. 
    Pool AH, Kvello P, Mann K, Cheung SK, Gordon MD et al. 2014. Four GABAergic interneurons impose feeding restraint in Drosophila. Neuron 83:164–77
    [Google Scholar]
  97. 97. 
    Yapici N, Cohn R, Schusterreiter C, Ruta V, Vosshall LB 2016. A taste circuit that regulates ingestion by integrating food and hunger signals. Cell 165:715–29
    [Google Scholar]
  98. 98. 
    Kain P, Dahanukar A. 2015. Secondary taste neurons that convey sweet taste and starvation in the Drosophila brain. Neuron 85:819–32
    [Google Scholar]
  99. 99. 
    White KE, Humphrey DM, Hirth F 2010. The dopaminergic system in the aging brain of Drosophila. Front. Neurosci 4:205
    [Google Scholar]
  100. 100. 
    Krashes MJ, DasGupta S, Vreede A, White B, Armstrong JD, Waddell S 2009. A neural circuit mechanism integrating motivational state with memory expression in Drosophila. Cell 139:416–27
    [Google Scholar]
  101. 101. 
    Albin SD, Kaun KR, Knapp J-M, Chung P, Heberlein U, Simpson JH 2015. A subset of serotonergic neurons evokes hunger in adult Drosophila. Curr. Biol 25:2435–40
    [Google Scholar]
  102. 102. 
    Zhan YP, Liu L, Zhu Y 2016. Taotie neurons regulate appetite in Drosophila. Nat. Commun 7:13633
    [Google Scholar]
  103. 103. 
    Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D 2015. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect. Psychol. Sci. 10:227–37
    [Google Scholar]
  104. 104. 
    Ong AD, Allaire JC. 2005. Cardiovascular intraindividual variability in later life: the influence of social connectedness and positive emotions. Psychol. Aging 20:476–85
    [Google Scholar]
  105. 105. 
    Brummett BH, Barefoot JC, Siegler IC, Clapp-Channing NE, Lytle BL et al. 2001. Characteristics of socially isolated patients with coronary artery disease who are at elevated risk for mortality. Psychosom. Med. 63:267–72
    [Google Scholar]
  106. 106. 
    Glass TA, Matchar DB, Belyea M, Feussner JR 1993. Impact of social support on outcome in first stroke. Stroke 24:64–70
    [Google Scholar]
  107. 107. 
    Fratiglioni L, Wang HX, Ericsson K, Maytan M, Winblad B 2000. Influence of social network on occurrence of dementia: a community-based longitudinal study. Lancet 355:1315–19
    [Google Scholar]
  108. 108. 
    Epel ES, Lithgow GJ. 2014. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity. J. Gerontol. A Biol. Sci. Med. Sci. 69:Suppl. 1S10–16
    [Google Scholar]
  109. 109. 
    Chetty R, Stepner M, Abraham S, Lin S, Scuderi B et al. 2016. The association between income and life expectancy in the United States, 2001–2014. JAMA 315:1750–66
    [Google Scholar]
  110. 110. 
    Dawson EH, Bailly TPM, Dos Santos J, Moreno C, Devilliers M et al. 2018. Social environment mediates cancer progression in Drosophila. Nat. Commun 9:3574
    [Google Scholar]
  111. 111. 
    Huang H, Wang L, Cao M, Marshall C, Gao J et al. 2015. Isolation housing exacerbates Alzheimer's disease-like pathophysiology in aged APP/PS1 mice. Int. J. Neuropsychopharmacol. 18: pyu116
    [Google Scholar]
  112. 112. 
    Mumtaz F, Khan MI, Zubair M, Dehpour AR 2018. Neurobiology and consequences of social isolation stress in animal model—a comprehensive review. Biomed. Pharmacother. 105:1205–22
    [Google Scholar]
  113. 113. 
    Razzoli M, Nyuyki-Dufe K, Gurney A, Erickson C, McCallum J et al. 2018. Social stress shortens lifespan in mice. Aging Cell 17:e12778
    [Google Scholar]
  114. 114. 
    Kuo TH, Yew JY, Fedina TY, Dreisewerd K, Dierick HA, Pletcher SD 2012. Aging modulates cuticular hydrocarbons and sexual attractiveness in Drosophila melanogaster. J. Exp. Biol 215:814–21
    [Google Scholar]
  115. 115. 
    Brennan PA, Kendrick KM. 2006. Mammalian social odours: attraction and individual recognition. Philos. Trans. R. Soc. B 361:2061–78
    [Google Scholar]
  116. 116. 
    Wang L, Anderson DJ. 2010. Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila. Nature 463:227–31
    [Google Scholar]
  117. 117. 
    Kurtovic A, Widmer A, Dickson BJ 2007. A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone. Nature 446:542–46
    [Google Scholar]
  118. 118. 
    Fedina TY, Kuo TH, Dreisewerd K, Dierick HA, Yew JY, Pletcher SD 2012. Dietary effects on cuticular hydrocarbons and sexual attractiveness in Drosophila. PLOS ONE 7:e49799
    [Google Scholar]
  119. 119. 
    Kuo TH, Fedina TY, Hansen I, Dreisewerd K, Dierick HA et al. 2012. Insulin signaling mediates sexual attractiveness in Drosophila. PLOS Genet 8:e1002684
    [Google Scholar]
  120. 120. 
    Yang CF, Shah NM. 2014. Representing sex in the brain, one module at a time. Neuron 82:261–78
    [Google Scholar]
  121. 121. 
    Henkel S, Setchell JM. 2018. Group and kin recognition via olfactory cues in chimpanzees (Pan troglodytes). Proc. R. Soc. B 285: https://doi.org/10.1098/rspb.2018.1527
    [Crossref] [Google Scholar]
  122. 122. 
    Lazaro-Perea C, Snowdon CT, Arruda MF 1999. Scent-making behavior in wild groups of common marmosets. Behav. Ecol. Sociobiol. 46:313–24
    [Google Scholar]
  123. 123. 
    Maures TJ, Booth LN, Benayoun BA, Izrayelit Y, Schroeder FC, Brunet A 2014. Males shorten the life span of C.elegans hermaphrodites via secreted compounds. Science 343:541–44
    [Google Scholar]
  124. 124. 
    Aprison EZ, Ruvinsky I. 2016. Sexually antagonistic male signals manipulate germline and soma of C.elegans hermaphrodites. Curr. Biol. 26:2827–33
    [Google Scholar]
  125. 125. 
    Harvanek ZM, Lyu Y, Gendron CM, Johnson JC, Kondo S et al. 2017. Perceptive costs of reproduction drive ageing and physiology in male Drosophila. Nat. Ecol. Evol 1:0152
    [Google Scholar]
  126. 126. 
    Flintham EO, Yoshida T, Smith S, Pavlou HJ, Goodwin SF et al. 2018. Interactions between the sexual identity of the nervous system and the social environment mediate lifespan in Drosophila melanogaster. Proc. R. Soc. B 285: https://doi.org/10.1098/rspb.2018.1450
    [Crossref] [Google Scholar]
  127. 127. 
    Uchino BN. 2006. Social support and health: a review of physiological processes potentially underlying links to disease outcomes. J. Behav. Med. 29:377–87
    [Google Scholar]
  128. 128. 
    Chen S, Lee AY, Bowens NM, Huber R, Kravitz EA 2002. Fighting fruit flies: a model system for the study of aggression. PNAS 99:5664–68
    [Google Scholar]
  129. 129. 
    Zelikowsky M, Hui M, Karigo T, Choe A, Yang B et al. 2018. The neuropeptide Tac2 controls a distributed brain state induced by chronic social isolation stress. Cell 173:1265–79.e19
    [Google Scholar]
  130. 130. 
    Liu G, Nath T, Linneweber GA, Claeys A, Guo Z et al. 2018. A simple computer vision pipeline reveals the effects of isolation on social interaction dynamics in Drosophila. PLOSComput. Biol 14:e1006410
    [Google Scholar]
  131. 131. 
    Liu H, Wang Z. 2005. Effects of social isolation stress on immune response and survival time of mouse with liver cancer. World J. Gastroenterol. 11:5902–4
    [Google Scholar]
  132. 132. 
    Karelina K, Norman GJ, Zhang N, Morris JS, Peng H, DeVries AC 2009. Social isolation alters neuroinflammatory response to stroke. PNAS 106:5895–900
    [Google Scholar]
  133. 133. 
    Dong H, Goico B, Martin M, Csernansky CA, Bertchume A, Csernansky JG 2004. Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 127:601–9
    [Google Scholar]
  134. 134. 
    Ruan H, Wu CF. 2008. Social interaction-mediated lifespan extension of Drosophila Cu/Zn superoxide dismutase mutants. PNAS 105:7506–10
    [Google Scholar]
  135. 135. 
    Ruland C, Berlandi J, Eikmeier K, Weinert T, Lin FJ et al. 2018. Decreased cerebral Irp-1B limits impact of social isolation in wild type and Alzheimer's disease modeled in Drosophila melanogaster. Genes Brain Behav 17:e12451
    [Google Scholar]
  136. 136. 
    Cacioppo JT, Cacioppo S, Capitanio JP, Cole SW 2015. The neuroendocrinology of social isolation. Annu. Rev. Psychol. 66:733–67
    [Google Scholar]
  137. 137. 
    Ganguly-Fitzgerald I, Donlea J, Shaw PJ 2006. Waking experience affects sleep need in Drosophila. Science 313:1775–81
    [Google Scholar]
  138. 138. 
    Shohat-Ophir G, Kaun KR, Azanchi R, Mohammed H, Heberlein U 2012. Sexual deprivation increases ethanol intake in Drosophila. Science 335:1351–55
    [Google Scholar]
  139. 139. 
    Alekseyenko OV, Chan YB, Fernandez MP, Bulow T, Pankratz MJ, Kravitz EA 2014. Single serotonergic neurons that modulate aggression in Drosophila.Curr. Biol 24:2700–7
    [Google Scholar]
  140. 140. 
    Dierick HA, Greenspan RJ. 2007. Serotonin and neuropeptide F have opposite modulatory effects on fly aggression. Nat. Genet. 39:678–82
    [Google Scholar]
  141. 141. 
    Hoyer SC, Eckart A, Herrel A, Zars T, Fischer SA et al. 2008. Octopamine in male aggression of Drosophila. Curr. Biol 18:159–67
    [Google Scholar]
  142. 142. 
    Luo J, Lushchak OV, Goergen P, Williams MJ, Nassel DR 2014. Drosophila insulin-producing cells are differentially modulated by serotonin and octopamine receptors and affect social behavior. PLOS ONE 9:e99732
    [Google Scholar]
  143. 143. 
    Mohawk JA, Green CB, Takahashi JS 2012. Central and peripheral circadian clocks in mammals. Annu. Rev. Neurosci. 35:445–62
    [Google Scholar]
  144. 144. 
    Tataroglu O, Emery P. 2015. The molecular ticks of the Drosophila circadian clock. Curr. Opin. Insect. Sci. 7:51–57
    [Google Scholar]
  145. 145. 
    Evans JA, Davidson AJ. 2013. Health consequences of circadian disruption in humans and animal models. Prog. Mol. Biol. Transl. Sci. 119:283–323
    [Google Scholar]
  146. 146. 
    James SM, Honn KA, Gaddameedhi S, Van Dongen HPA 2017. Shift work: disrupted circadian rhythms and sleep-implications for health and well-being. Curr. Sleep Med. Rep. 3:104–12
    [Google Scholar]
  147. 147. 
    Yoshii T, Heshiki Y, Ibuki-Ishibashi T, Matsumoto A, Tanimura T, Tomioka K 2005. Temperature cycles drive Drosophila circadian oscillation in constant light that otherwise induces behavioural arrhythmicity. Eur. J. Neurosci. 22:1176–84
    [Google Scholar]
  148. 148. 
    Oike H, Sakurai M, Ippoushi K, Kobori M 2015. Time-fixed feeding prevents obesity induced by chronic advances of light/dark cycles in mouse models of jet-lag/shift work. Biochem. Biophys. Res. Commun. 465:556–61
    [Google Scholar]
  149. 149. 
    Videnovic A, Klerman EB, Zee PC 2017. Light therapy promoting dopamine release by stimulating retina in Parkinson disease-reply. JAMA Neurol 74:1268–69
    [Google Scholar]
  150. 150. 
    Koh K, Evans JM, Hendricks JC, Sehgal A 2006. A Drosophila model for age-associated changes in sleep:wake cycles. PNAS 103:13843–47
    [Google Scholar]
  151. 151. 
    Nakamura TJ, Nakamura W, Yamazaki S, Kudo T, Cutler T et al. 2011. Age-related decline in circadian output. J. Neurosci. 31:10201–5
    [Google Scholar]
  152. 152. 
    Buysse DJ, Monk TH, Carrier J, Begley A 2005. Circadian patterns of sleep, sleepiness, and performance in older and younger adults. Sleep 28:1365–76
    [Google Scholar]
  153. 153. 
    Luo W, Chen WF, Yue Z, Chen D, Sowcik M et al. 2012. Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations. Aging Cell 11:428–38
    [Google Scholar]
  154. 154. 
    Rakshit K, Krishnan N, Guzik EM, Pyza E, Giebultowicz JM 2012. Effects of aging on the molecular circadian oscillations in Drosophila. Chronobiol. Int 29:5–14
    [Google Scholar]
  155. 155. 
    Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T et al. 2015. Age-related changes in the circadian system unmasked by constant conditions. eNeuro 2:e0064–15.2015
    [Google Scholar]
  156. 156. 
    Li H, Satinoff E. 1998. Fetal tissue containing the suprachiasmatic nucleus restores multiple circadian rhythms in old rats. Am. J. Physiol. 275:R1735–44
    [Google Scholar]
  157. 157. 
    Hurd MW, Ralph MR. 1998. The significance of circadian organization for longevity in the golden hamster. J. Biol. Rhythms. 13:430–36
    [Google Scholar]
  158. 158. 
    Krishnan N, Kretzschmar D, Rakshit K, Chow E, Giebultowicz JM 2009. The circadian clock gene period extends healthspan in aging Drosophila melanogaster. Aging 1:937–48
    [Google Scholar]
  159. 159. 
    Krishnan N, Davis AJ, Giebultowicz JM 2008. Circadian regulation of response to oxidative stress in Drosophila melanogaster. Biochem. Biophys. Res. Commun 374:299–303
    [Google Scholar]
  160. 160. 
    Solovev I, Shegoleva E, Fedintsev A, Shaposhnikov M, Moskalev A 2019. Circadian clock genes’ overexpression in Drosophila alters diet impact on lifespan. Biogerontology 20:159–70
    [Google Scholar]
  161. 161. 
    Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T et al. 2016. Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in Drosophila. Cell Metab 23:143–54
    [Google Scholar]
  162. 162. 
    Ulgherait M, Chen A, Oliva MK, Kim HX, Canman JC et al. 2016. Dietary restriction extends the lifespan of circadian mutants tim and per. Cell Metab 24:763–64
    [Google Scholar]
  163. 163. 
    Hendricks JC, Lu S, Kume K, Yin JC, Yang Z, Sehgal A 2003. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster. J. Biol. Rhythms 18:12–25
    [Google Scholar]
  164. 164. 
    Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP 2006. Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20:1868–73
    [Google Scholar]
  165. 165. 
    McDearmon EL, Patel KN, Ko CH, Walisser JA, Schook AC et al. 2006. Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science 314:1304–8
    [Google Scholar]
  166. 166. 
    Hughes ME, Hong HK, Chong JL, Indacochea AA, Lee SS et al. 2012. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue. PLOS Genet 8:e1002835
    [Google Scholar]
  167. 167. 
    Rakshit K, Giebultowicz JM. 2013. Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila. Aging Cell 12:752–62
    [Google Scholar]
  168. 168. 
    Anderson JR. 2016. Comparative thanatology. Curr. Biol. 26:R553–56
    [Google Scholar]
  169. 169. 
    Chakraborty TS, Gendron CM, Lyu Y, Munneke AS, DeMarco MN et al. 2019. Sensory perception of dead conspecifics induces aversive cues and modulates lifespan through serotonin in Drosophila. Nat. Commun 10:2365
    [Google Scholar]
  170. 170. 
    Petrie K, Milligan-Saville J, Gayed A, Deady M, Phelps A et al. 2018. Prevalence of PTSD and common mental disorders amongst ambulance personnel: a systematic review and meta-analysis. Soc. Psychiatry Psychiatr. Epidemiol. 53:897–909
    [Google Scholar]
  171. 171. 
    Smith TC, Ryan MA, Wingard DL, Slymen DJ, Sallis JF et al. 2008. New onset and persistent symptoms of post-traumatic stress disorder self reported after deployment and combat exposures: prospective population based US military cohort study. BMJ 336:366–71
    [Google Scholar]
  172. 172. 
    Liu Z, Kariya MJ, Chute CD, Pribadi AK, Leinwand SG et al. 2018. Predator-secreted sulfolipids induce defensive responses in C. elegans. Nat. Commun 9:1128
    [Google Scholar]
  173. 173. 
    Zhou Y, Loeza-Cabrera M, Liu Z, Aleman-Meza B, Nguyen JK et al. 2017. Potential nematode alarm pheromone induces acute avoidance in Caenorhabditiselegans. Genetics 206:1469–78
    [Google Scholar]
  174. 174. 
    Bishop NA, Guarente L. 2007. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–49
    [Google Scholar]
  175. 175. 
    Zhang B, Gong J, Zhang W, Xiao R, Liu J, Xu XZS 2018. Brain-gut communications via distinct neuroendocrine signals bidirectionally regulate longevity in C. elegans. Genes Dev 32:258–70
    [Google Scholar]
  176. 176. 
    Kacsoh BZ, Bozler J, Ramaswami M, Bosco G 2015. Social communication of predator-induced changes in Drosophila behavior and germ line physiology. eLife 4:e07423
    [Google Scholar]
  177. 177. 
    Pereira AG, Moita MA. 2016. Is there anybody out there? Neural circuits of threat detection in vertebrates. Curr. Opin. Neurobiol. 41:179–87
    [Google Scholar]
  178. 178. 
    Perez-Gomez A, Bleymehl K, Stein B, Pyrski M, Birnbaumer L et al. 2015. Innate predator odor aversion driven by parallel olfactory subsystems that converge in the ventromedial hypothalamus. Curr. Biol. 25:1340–46
    [Google Scholar]
  179. 179. 
    Gross CT, Canteras NS. 2012. The many paths to fear. Nat. Rev. Neurosci. 13:651–58
    [Google Scholar]
  180. 180. 
    Martinez RC, Carvalho-Netto EF, Ribeiro-Barbosa ER, Baldo MV, Canteras NS 2011. Amygdalar roles during exposure to a live predator and to a predator-associated context. Neuroscience 172:314–28
    [Google Scholar]
  181. 181. 
    McDonald AJ. 1998. Cortical pathways to the mammalian amygdala. Prog. Neurobiol. 55:257–332
    [Google Scholar]
  182. 182. 
    Vyas S, Rodrigues AJ, Silva JM, Tronche F, Almeida OF et al. 2016. Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration. Neural Plast 2016:6391686
    [Google Scholar]
  183. 183. 
    Hanson JL, Hurley LM. 2014. Context-dependent fluctuation of serotonin in the auditory midbrain: the influence of sex, reproductive state and experience. J. Exp. Biol. 217:526–35
    [Google Scholar]
  184. 184. 
    Petrascheck M, Ye X, Buck LB 2007. An antidepressant that extends lifespan in adult Caenorhabditiselegans. Nature 450:553–56
    [Google Scholar]
  185. 185. 
    Burkewitz K, Morantte I, Weir HJM, Yeo R, Zhang Y et al. 2015. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell 160:842–55
    [Google Scholar]
  186. 186. 
    Domingos AI, Vaynshteyn J, Voss HU, Ren X, Gradinaru V et al. 2011. Leptin regulates the reward value of nutrient. Nat. Neurosci. 14:1562–68
    [Google Scholar]
  187. 187. 
    You YJ, Kim J, Raizen DM, Avery L 2008. Insulin, cGMP, and TGF-β signals regulate food intake and quiescence in C.elegans: a model for satiety. Cell Metab 7:249–57
    [Google Scholar]
  188. 188. 
    Teff K. 2000. Nutritional implications of the cephalic-phase reflexes: endocrine responses. Appetite 34:206–13
    [Google Scholar]
  189. 189. 
    Christakis NA, Fowler JH. 2007. The spread of obesity in a large social network over 32 years. N. Engl. J. Med. 357:370–79
    [Google Scholar]
  190. 190. 
    Anderson DJ, Adolphs R. 2014. A framework for studying emotions across species. Cell 157:187–200
    [Google Scholar]
/content/journals/10.1146/annurev-physiol-021119-034440
Loading
/content/journals/10.1146/annurev-physiol-021119-034440
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error