Physiological Resilience and the Impact on Health

  • N. Jennifer KlinedinstEmail author
  • Alisha Hackney


Resilience in aging is the ability to recover from or adapt to stress and maintain or restore one’s physical, psychological, or emotional equilibrium. While psychological resilience has been much of the focus in aging, increasing evidence suggests resilience in aging is a biopsychosocial phenomenon. The human lifespan is fraught with environmental, physical, and psychosocial challenges that result in a physiological response. This chapter presents biological aspects of resilience including a discussion of the hypothalamic-pituitary-adrenocortical (HPA) axis, neurochemicals, genetic, genomic and epigenetic influences, inflammation, oxidative stress, microbiome and immunity. Interventions to increase physiological resilience in aging include regular physical exercise, a low calorie high nutrient diet, prebiotics and probiotics and at the core, psychological and environmental stress reduction throughout the lifespan.


Resilience Stress Physiological resilience Neurochemicals Genetics 


  1. Agbedia, O. O., Varma, V., Seplaki, C. L., Seeman, T., Fried, L. P., Li, L., et al. (2011). Blunted diurnal decline of cortisol among older adults with low socioeconomic status. Annals of the New York Academy of Sciences, 1231, 56–64. Scholar
  2. Aguilera, G. (2011). HPA axis responsiveness to stress: Implications for healthy aging. Experimental Gerontology, 46(2), 90–95. Scholar
  3. Allen, J. M., Berg Miller, M. E., Pence, B. D., Whitlock, K., Nehra, V., Gaskins, H. R., et al. (2015). Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6 J mice. Journal of Applied Physiology, 118(8), 1059–1066. Scholar
  4. Alvarado, C., Álvarez, P., Puerto, M., Gausserès, N., Jiménez, L., & De la Fuente, M. (2006). Dietary supplementation with antioxidants improves functions and decreases oxidative stress of leukocytes from prematurely aging mice. Nutrition, 22(7–8), 767–777. Scholar
  5. Ancelin, M. L., & Ryan, J. (2017). 5-HTTLPR × stress hypothesis: Is the debate over? [Letter to the Editor]. Molecular Psychiatry. Scholar
  6. Azeredo, L. A. d., De Nardi, T., Levandowski, M. L., Tractenberg, S. G., Kommers-Molina, J., Wieck, A., … Grassi-Oliveira, R. (2017). The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults. Revista Brasileira de Psiquiatria, 39, 90–94.CrossRefGoogle Scholar
  7. Bäckman, L., Nyberg, L., Lindenberger, U., Li, S.-C., & Farde, L. (2006). The correlative triad among aging, dopamine, and cognition: Current status and future prospects. Neuroscience and Biobehavioral Reviews, 30(6), 791–807. Scholar
  8. Barbagallo, M., & Dominguez, L. J. (2010). Magnesium and aging. Current Pharmaceutical Design, 16(7), 832–839. Scholar
  9. Baylis, D., Bartlett, D. B., Patel, H. P., & Roberts, H. C. (2013). Understanding how we age: Insights into inflammaging. Longevity & Healthspan, 2(1). Scholar
  10. Beto, J. A. (2015). The role of calcium in human aging. Clinical Nutrition Research, 4(1), 1–8. Scholar
  11. Biagi, E., Candela, M., Fairweather-Tait, S., Franceschi, C., & Brigidi, P. (2012). Ageing of the human metaorganism: The microbial counterpart. Age, 34(1), 247–267. Scholar
  12. Bickford, P. C., Flowers, A., & Grimmig, B. (2017). Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases. Experimental Gerontology, 94, 4–8. Scholar
  13. Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., et al. (2014). Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterology, 14(1), 189.CrossRefGoogle Scholar
  14. Block, G., Jensen, C. D., Dalvi, T. B., Norkus, E. P., Crawford, P. B., Holland, N., et al. (2009). Vitamin C treatment reduces elevated c-reactive protein. Free Radical Biology and Medicine, 46(1), 70–77. Scholar
  15. Bolland, M. J., Grey, A., Gamble, G. D., & Reid, I. R. (2014a). The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: A trial sequential meta-analysis. The Lancet Diabetes & Endocrinology, 2(4), 307–320. Scholar
  16. Bolland, M. J., Grey, A., Gamble, G. D., & Reid, I. R. (2014b). Vitamin D supplementation and falls: A trial sequential meta-analysis. The Lancet Diabetes & Endocrinology, 2(7), 573–580. Scholar
  17. Bouayed, J., Rammal, H., & Soulimani, R. (2009). Oxidative stress and anxiety: Relationship and cellular pathways. Oxidative Medicine and Cellular Longevity, 2(2), 63–67. Scholar
  18. Bouzid, M. A., Filaire, E., McCall, A., & Fabre, C. (2015). Radical oxygen species, exercise and aging: An update. Sports Medicine, 45(9), 1245–1261.CrossRefGoogle Scholar
  19. Bowes, L., & Jaffee, S. R. (2013). Biology, genes, and resilience: Toward a multidisciplinary approach. Trauma, Violence, & Abuse, 14(3), 195–208. Scholar
  20. Bradley, R. G., Binder, E. B., Epstein, M. P., et al. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65(2), 190–200. Scholar
  21. Brestoff, J. R., & Artis, D. (2013). Commensal bacteria at the interface of host metabolism and the immune system. Nature Reviews Immunology, 14(7), 676–684. Scholar
  22. Buchman, A. S., Yu, L., Boyle, P. A., Schneider, J. A., De Jager, P. L., & Bennett, D. A. (2016). Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. Neurology, 86(8), 735–741. Scholar
  23. Buford, T. W. (2017). (Dis)trust your gut: The gut microbiome in age-related inflammation, health, and disease. Microbiome, 5(1).
  24. Calder, P. C., Alberts, R., Antoine, J. M., Blum, S. S., Bourded-Sicard, R., Ferns, G. A., … Al, E. (2009). Inflammatory disease processes and interactions with nutrition. British Journal of Nutrition, 101(Supplement S1).CrossRefGoogle Scholar
  25. Cámara, R. J. A., Gander, M.-L., Begré, S., & von Känel, R. (2011). Post-traumatic stress in Crohn’s disease and its association with disease activity. Frontline Gastroenterology, 2(1), 2–9. Scholar
  26. Campbell, S. C., Wisniewski, P. J., Noji, M., McGuinness, L. R., Häggblom, M. M., Lightfoot, S. A., et al. (2016). The effect of diet and exercise on intestinal integrity and microbial diversity in mice. PLoS ONE, 11(3), 1–17. Scholar
  27. Cannizzo, E. S., Clement, C. C., Sahu, R., Follo, C., & Santambrogio, L. (2011). Oxidative stress, inflammaging, and immunosenescence. Journal of Proteomics, 74, 2313–2323. Scholar
  28. Chan, S., & Debono, M. (2010). Replication of cortisol circadian rhythm: New advances in hydrocortisone replacement therapy. Therapeutic Advances in Endocrinology and Metabolism, 1(3), 129–138. Scholar
  29. Charney, D. S. (2004). Psychobiological mechanisms of resilience and vulnerability. Focus, 2(4), 368–391. Scholar
  30. Claesson, M. J., Cusack, S., O’Sullivan, O., Greene-Diniz, R., de Weerd, H., Flannery, E., et al. (2011). Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proceedings of the National Academy of Sciences, 108(Supplement 1), 4586–4591. Scholar
  31. Cohen, H., Ziv, Y., Cardon, M., Kaplan, Z., Matar, M. A., Gidron, Y., et al. (2006). Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+ CD25+ cells. Journal of Neurobiology, 66(6), 552–563. Scholar
  32. Conner, E. M., & Grisham, M. B. (1996). Inflammation, free radicals and antioxidants. Nutrition, 12(4), 274–277. Scholar
  33. Cryan, J. F., & Dinan, T. G. (2012). Mind-alerting microorganisms: The impact of the gut microbiota on brain and behavior. Nature Reviews Neuroscience, 13, 701–712. Scholar
  34. Culverhouse, R., Saccone, N., Horton, A., Ma, Y., Anstey, K., Banaschewski, T., … Fisher, H. (2017). Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry.Google Scholar
  35. Dato, S., Crocco, P., D’Aquila, P., de Rango, F., Bellizzi, D., … Passarino, G. (2013). Exploring the role of genetic variability and lifestyle in oxidative stress response for healthy aging and longevity. International Journal of Molecular Sciences, 14(8), 16443.CrossRefGoogle Scholar
  36. Davis, C., Bryan, J., Hodgson, J., & Murphy, K. (2015). Definition of the mediterranean diet: A literature review. Nutrients, 7(11), 9139–9153. Scholar
  37. De la Fuente, M., & Miquel, J. (2009). An update of the oxidation-inflammation theory of aging: The involvement of the immune system in oxi-inflamm-aging. Current Pharmaceutical Design, 15(26), 3003–3026.CrossRefGoogle Scholar
  38. de Roos, B., & Duthie, G. G. (2015). Role of dietary pro-oxidants in the maintenance of health and resilience to oxidative stress. Molecular Nutrition & Food Research, 59(7), 1229–1248. Scholar
  39. Dijckmans, B., Tortosa-Martínez, J., Caus, N., González-Caballero, G., Martínez-Pelegrin, B., Manchado-Lopez, C., et al. (2017). Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults? European Review of Aging and Physical Activity, 14(1), 6.CrossRefGoogle Scholar
  40. Ding, Y.-H., Young, C. N., Luan, X., Li, J., Rafols, J. A., Clark, J. C., et al. (2005). Exercise preconditioning ameliorates inflammatory injury in ischemic rats during reperfusion. Acta Neuropathologica, 109(3), 237–246.CrossRefGoogle Scholar
  41. Dröge, W., & Schipper, H. M. (2007). Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell, 6(3), 361–370. Scholar
  42. Enman, N. M., Sabban, E. L., McGonigle, P., & Van Bockstaele, E. J. (2015). Targeting the neuropeptide Y system in stress-related psychiatric disorders. Neurobiology of Stress, 1, 33–43. Scholar
  43. Ermak, G., & Davies, K. J. A. (2002). Calcium and oxidative stress: From cell signaling to cell death. Molecular Immunology, 38(10), 713–721. Scholar
  44. Evans, C. C., LePard, K. J., Kwak, J. W., Stancukas, M. C., Laskowski, S., Dougherty, J., … Ciancio, M. J. (2014). Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PLoS ONE, 9(3). Scholar
  45. Fagundes, C. P., Gillie, B. L., Derry, H. M., Bennett, J. M., & Kiecolt-Glaser, J. K. (2012). Chapter 2: Resilience and immune function in older adults. Annual Review of Gerontology and Geriatrics, 32(1), 29–48. Scholar
  46. Feder, A., Nestler, E. J., & Charney, D. S. (2009). Psychobiology and molecular genetics of resilience. Nature Reviews Neuroscience, 10(6), 446–457.CrossRefGoogle Scholar
  47. Finkel, T., & Holbrook, N. J. (2000). Oxidants, oxidative stress and the biology of ageing. Nature, 408, 239–247.CrossRefGoogle Scholar
  48. Ford, E. S., Liu, S., Mannino, D. M., Giles, W. H., & Smith, S. J. (2003). C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. European Journal of Clinical Nutrition, 57(9), 1157–1163. Scholar
  49. Ford, E. S., & Mokdad, A. H. (2003). Dietary magnesium intake in a national sample of US adults. The Journal of Nutrition, 133(9), 2879–2882.CrossRefGoogle Scholar
  50. Foster, J. A., & McVey Neufeld, K. A. (2013). Gut-brain axis: How the microbiome influences anxiety and depression. Trends in Neurosciences, 36(5), 305–312. Scholar
  51. Franceschi, C., & Campisi, J. (2014). Chronic inflammation (Inflammaging) and its potential contribution to age-associated diseases. Journals of Gerontology Series A, 69(S1), S4–S9. Scholar
  52. Franceschi, C., Garagnani, P., Vitale, G., & Capri, M. (2017). Inflammaging and ‘garb-aging’. Trends in Endocrinology and Metabolism, 28(3), 199–212. Scholar
  53. Franceschi, C., Monti, D., Sansoni, P., & Cossarizza, A. (1995). The immunology of exceptional individuals: The lesson of centenarians. Immunology Today, 16(1), 12–16. Scholar
  54. Franco, O. H., Karnik, K., Osborne, G., Ordovas, J. M., Catt, M., & van der Ouderaa, F. (2009). Changing course in ageing research: The healthy ageing phenotype. Maturitas, 63(1), 13–19. Scholar
  55. Franz, C. E., O’Brien, R. C., Hauger, R. L., Mendoza, S. P., Panizzon, M. S., Prom-Wormley, E., et al. (2011). Cross-sectional and 35-year longitudinal assessment of salivary cortisol and cognitive functioning: The Vietnam era twin study of aging. Psychoneuroendocrinology, 36(7), 1040–1052. Scholar
  56. Fuentes, E., Fuentes, M., Alarcón, M., & Palomo, I. (2017). Immune system dysfunction in the elderly. Anais da Academia Brasileira de Ciências, 89(1), 285–299. Scholar
  57. Gaffey, A. E., Bergeman, C. S., Clark, L. A., & Wirth, M. M. (2016). Aging and the HPA axis: Stress and resilience in older adults. Neuroscience & Biobehavioral Reviews, 68((Supplement C)), 928–945. Scholar
  58. Gardner, M. P., Lightman, S., Sayer, A. A., Cooper, C., Cooper, R., Deeg, D., et al. (2013). Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis. Psychoneuroendocrinology, 38(1), 40–49. Scholar
  59. Gillespie, C. F., Phifer, J., Bradley, B., & Ressler, K. J. (2009). Risk and resilience: Genetic and environmental influences on development of the stress response. Depression and Anxiety, 26(11), 984–992. Scholar
  60. Giugliano, D., Ceriello, A., & Esposito, K. (2006). The effects of diet on inflammation: Emphasis on the metabolic syndrome. Journal of the American College of Cardiology, 48(4), 677–685. Scholar
  61. Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. A. (2008). Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: Possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain, Behavior, and Immunity, 22(3), 354–366. Scholar
  62. Gowda, U., Mutowo, M. P., Smith, B. J., Wluka, A. E., & Renzaho, A. M. (2015). Vitamin D supplementation to reduce depression in adults: Meta-analysis of randomized controlled trials. Nutrition, 31(3), 421–429.CrossRefGoogle Scholar
  63. Gu, Y., Dee, C. M., & Shen, J. (2011). Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability. Frontiers in Bioscience, S3, 1216–1231.CrossRefGoogle Scholar
  64. Gupta, D., & Morley, J. E. (2011). Hypothalamic-pituitary-adrenal (HPA) axis and aging Comprehensive Physiology. Wiley.Google Scholar
  65. Hatzinger, M., Brand, S., Herzig, N., & Holsboer-Trachsler, E. (2011). In healthy young and elderly adults, hypothalamic-pituitary-adrenocortical axis reactivity (HPA AR) varies with increasing pharmacological challenge and with age, but not with gender. Journal of Psychiatric Research, 45(10), 1373–1380. Scholar
  66. Heidt, T., Sager, H. B., Courties, G., Dutta, P., Iwamoto, Y., Zaltsman, A., et al. (2014). Chronic variable stress activates hematopoietic stem cells. Nature Medicine, 20(7), 754–758. Scholar
  67. Henningsen, K., Palmfeldt, J., Christiansen, S., Baiges, I., Bak, S., Jensen, O. N., … Wiborg, O. (2012). Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression. Molecular & Cellular Proteomics, 11(7). Scholar
  68. Hodes, G. E., Pfau, M. L., Leboeuf, M., Golden, S. A., Christoffel, D. J., Bregman, D., et al. (2014). Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proceedings of the National Academy of Sciences, 111(45), 16136–16141. Scholar
  69. Hoffman-Goetz, L., Pervaiz, N., & Guan, J. (2009). Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-α in intestinal lymphocytes. Brain, Behavior, and Immunity, 23(4), 498–506. Scholar
  70. Hoffman-Goetz, L., Pervaiz, N., Packer, N., & Guan, J. (2010). Freewheel training decreases pro- and increases anti-inflammatory cytokine expression in mouse intestinal lymphocytes. Brain, Behavior, and Immunity, 24(7), 1105–1115. Scholar
  71. Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jacan, A., & Reichmann, F. (2017). Visceral inflammation and immune activation stress the brain. Frontiers in Immunology, 8.
  72. Hosang, G. M., Shiles, C., Tansey, K. E., McGuffin, P., & Uher, R. (2014). Interaction between stress and the BDNF Val66Met polymorphism in depression: A systematic review and meta-analysis. BMC Medicine, 12, 7. Scholar
  73. Hroudová, J., Fišar, Z., Kitzlerová, E., Zvěřová, M., & Raboch, J. (2013). Mitochondrial respiration in blood platelets of depressive patients. Mitochondrion, 13(6), 795–800.CrossRefGoogle Scholar
  74. Ising, M., Depping, A.-M., Siebertz, A., Lucae, S., Unschuld, P. G., Kloiber, S., et al. (2008). Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. European Journal of Neuroscience, 28(2), 389–398. Scholar
  75. Karatsoreos, I. N., & McEwen, B. S. (2011). Psychobiological allostasis: Resistance, resilience and vulnerability. Trends in Cognitive Sciences, 15(12), 576–584. Scholar
  76. Killilea, D. W., & Maier, J. A. (2008). A connection between magnesium deficiency and aging: New insights from cellular studies. Magnesium Research, 21(2), 77–82.PubMedPubMedCentralGoogle Scholar
  77. Kim, Y., McGee, S., Czeczor, J., Walker, A., Kale, R., Kouzani, A., et al. (2016). Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: Alterations in mitochondrial function relate to antidepressant-like effects. Translational psychiatry, 6(6), e842.CrossRefGoogle Scholar
  78. Klinedinst, N. J., & Regenold, W. T. (2015). A mitochondrial bioenergetic basis of depression. Journal of Bioenergetics and Biomembranes, 47(1–2), 155–171.CrossRefGoogle Scholar
  79. Klinedinst, N. J., Resnick, B., Yerges-Armstrong, L. M., & Dorsey, S. G. (2015). The interplay of genetics, behavior, and pain with depressive symptoms in the elderly. The Gerontologist, 55(Suppl-1), S67–S77.CrossRefGoogle Scholar
  80. Kohut, M. L., Arntson, B. A., Lee, W., Rozeboom, K., Yoon, K.-J., Cunnick, J. E., et al. (2004). Moderate exercise improves antibody response to influenza immunization in older adults. Vaccine, 22(17), 2298–2306. Scholar
  81. Koo, J. W., & Duman, R. S. (2008). IL-1 is an essential mediator of the antineurogenic and anhedonic effects of stress. Proceedings of the National Academy of Sciences, 105(2), 751–756. Scholar
  82. Lanquillon, S., Krieg, J. C., Bening-Abu-Shach, U., & Vedder, H. (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology, 22(99), 370–379. Scholar
  83. Larbi, A., Rymkiewicz, P., Vasudev, A., Low, I., Shadan, N. B., Mustafah, S., et al. (2013). The immune system in the elderly: A fair fight against diseases? Aging and Health, 9(1), 35–47. Scholar
  84. Lenze, E. J., Shardell, M., Ferrell, R. E., Orwig, D., Yu-Yahiro, J., Hawkes, W., et al. (2008). Association of serotonin-1A and 2A receptor promoter polymorphisms with depressive symptoms and functional recovery in elderly persons after hip fracture. Journal of Affective Disorders, 111(1), 61–66. Scholar
  85. Lewitus, G. M., & Schwartz, M. (2009). Behavioral immunization: Immunity to self-antigens contributes to psychological stress resilience. Molecular Psychiatry, 14(5), 532–536. Scholar
  86. Lindqvist, D., Wolkowitz, O. M., Mellon, S., Yehuda, R., Flory, J. D., Henn-Haase, C., et al. (2014). Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. Brain, Behavior, and Immunity, 42, 81–88. Scholar
  87. Lyte, M., Li, W., Opitz, N., Gaykema, R. P. A., & Goehler, L. E. (2006). Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiology & Behavior, 89(3), 350–357. Scholar
  88. Maes, M., Van der Planken, M., Stevens, W. J., Peeters, D., DeClerck, L. S., Bridts, C. H., et al. (1992). Leukocytosis, monocytosis and neutrophilia: Hallmarks of severe depression. Journal of Psychiatric Research, 26(2), 125–134.CrossRefGoogle Scholar
  89. Manji, H., Kato, T., Di Prospero, N. A., Ness, S., Beal, M. F., Krams, M., et al. (2012). Impaired mitochondrial function in psychiatric disorders. Nature Reviews Neuroscience, 13(5), 293–307.CrossRefGoogle Scholar
  90. Masood, A., Nadeem, A., Mustafa, S. J., & O’Donnell, J. M. (2008). Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice. Journal of Pharmacology and Experimental Therapeutics, 326(2), 369–379. Scholar
  91. Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., et al. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 110(20), 8302–8307.CrossRefGoogle Scholar
  92. Ménard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. (2017). Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropscyhopharmacoloy Reviews, 42, 62–80. Scholar
  93. Mika, A., Van Treuren, W., González, A., Herrera, J. J., Knight, R., & Fleshner, M. (2015). Exercise is more effective at altering gut microbial composition and producing stable changes in lean mass in juvenile versus adult male F344 rats. PLoS ONE, 10(5), 1–20. Scholar
  94. Miller, B. F., Seals, D. R., & Hamilton, K. L. (2017). A viewpoint on considering physiological principles to study stress resistance and resilience with aging. Ageing Research Reviews, 38(Supplement C), 1–5. Scholar
  95. Morgan, C. A., Wang, S., Southwick, S. M., Rasmusson, A., Hazlett, G., Hauger, R. L., et al. (2000). Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biological Psychiatry, 47(10), 902–909. Scholar
  96. Morley, J. E. (2012). Anorexia of aging: A true geriatric syndrome. The Journal of Nutrition, Health & Aging, 16(5), 422–425.CrossRefGoogle Scholar
  97. Moro-García, M. A., Fernández-García, B., Echeverría, A., Rodríguez-Alonso, M., Suárez-García, F. M., Solano-Jaurrieta, J. J., et al. (2014). Frequent participation in high volume exercise throughout life is associated with a more differentiated adaptive immune response. Brain, Behavior, and Immunity, 39, 61–74. Scholar
  98. Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., & Ustun, B. (2007). Depression, chronic diseases, and decrements in health: Results from the World Health Surveys. The Lancet, 370(9590), 851–858. Scholar
  99. Neufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011). Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterology and Motility, 23(3), 255–265. Scholar
  100. Neufer, P. D., Bamman, M. M., Muoio, D. M., Bouchard, C., Cooper, D. M., Goodpaster, B. H., et al. (2015). Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metabolism, 22(1), 4–11.CrossRefGoogle Scholar
  101. Nguyen, T., Nioi, P., & Pickett, C. B. (2009). The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. The Journal of Biological Chemistry, 284(20), 13291–13295. Scholar
  102. Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., et al. (2012). Host-gut microbiota metabolic interactions. Science, 336(June), 1262–1268. Scholar
  103. Nickerson, M., Elphick, G., Campisi, J., Greenwood, B., & Fleshner, M. (2005). Physical activity alters the brain Hsp72 and IL-1β responses to peripheral E. coli challenge. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 289(6), R1665–R1674.CrossRefGoogle Scholar
  104. O’Donovan, A. (2016). PTSD is associated with elevated inflammation. Any impact on clinical practice? Evidence Based Mental Health, 19(4). Scholar
  105. O’Hara, R., Marcus, P., Thompson, W. K., Flournoy, J., Vahia, I., Lin, X., et al. (2012). 5-HTTLPR short allele, resilience, and successful aging in older adults. The American Journal of Geriatric Psychiatry, 20(5), 452–456.CrossRefGoogle Scholar
  106. O’Mahony, S., Clarke, G., Borre, Y., Dinan, T., & Cryan, J. (2015). Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural Brain Research, 277, 32–48.CrossRefGoogle Scholar
  107. Pascoe, A. R., Fiatarone Singh, M. A., & Edwards, K. M. (2014). The effects of exercise on vaccination responses: A review of chronic and acute exercise interventions in humans. Brain, Behavior, and Immunity, 39, 33–41. Scholar
  108. Perroud, N., Paoloni-Giacobino, A., Prada, P., Olié, E., Salzmann, A., Nicastro, R., et al. (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Translational psychiatry, 1(12), e59.CrossRefGoogle Scholar
  109. Pfau, M. L., & Russo, S. J. (2015). Peripheral and central mechanisms of stress resilience. Neurobiology of Stress, 66–79. Scholar
  110. Polanczyk, G., Caspi, A., Williams, B., et al. (2009). Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension. Archives of General Psychiatry, 66(9), 978–985. Scholar
  111. Powell, N. D., Sloan, E. K., Bailey, M. T., Arevalo, J. M. G., Miller, G. E., Chen, E., et al. (2013). Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proceedings of the National Academy of Sciences, 110(41), 16574–16579. Scholar
  112. Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., et al. (2014). Oxidative stress, prooxidants, and antioxidants: The interplay. BioMed Research International, 2014. Scholar
  113. Rammal, H., Bouayed, J., Younos, C., & Soulimani, R. (2008). Evidence that oxidative stress is linked to anxiety-related behaviour in mice. Brain, Behavior, and Immunity, 22(8), 1156–1159. Scholar
  114. Reber, S. O., Siebler, P. H., Donner, N. C., Morton, J. T., Smith, D. G., Kopelman, J. M., et al. (2016). Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proceedings of the National Academy of Sciences, 113(22), E3130–E3139. Scholar
  115. Resnick, B., Klinedinst, N. J., Yerges-Armstrong, L., Choi, E. Y., & Dorsey, S. G. (2015). The impact of genetics on physical resilience and successful aging. Journal of aging and health, 27(6), 1084–1104.CrossRefGoogle Scholar
  116. Rook, G. A. W., Raison, C. L., & Lowry, C. A. (2014). Microbial ‘old friends’, immunoregulation and socioeconomic status. Clinical and Experimental Immunology, 177(1), 1–12. Scholar
  117. Rothman, S. M., & Mattson, M. P. (2013). Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan. Neuroscience, 239, 228–240. Scholar
  118. Rutherford, B. R., Taylor, W. D., Brown, P. J., Sneed, J. R., & Roose, S. P. (2016). Biological aging and the future of geriatric psychiatry. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(3), 343–352.Google Scholar
  119. Salim, S. (2017). Oxidative stress and the central nervous system. Journal of Pharmacology and Experimental Therapeutics, 360, 201–205. Scholar
  120. Sallam, N., & Laher, I. (2016). Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases. Oxidative Medicine and Cellular Longevity, 2016. Scholar
  121. Sansoni, P., Cossarizza, A., Brianti, V., Fagnoni, F., Snelli, G., Monti, D., et al. (1993). Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood, 82(9), 2767–2773.PubMedGoogle Scholar
  122. Santoro, A., Pini, E., Scurti, M., Palmas, G., Berendsen, A., Brzozowska, A., et al. (2014). Combating inflammaging through a Mediterranean whole diet approach: The NU-AGE project’s conceptual framework and design. Mechanisms of Ageing and Development, 136–137, 3–13. Scholar
  123. Sartori, S. B., Whittle, N., Hetzenauer, A., & Singewald, N. (2012). Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. Neuropharmacology, 62(1), 304–312. Scholar
  124. Schiavone, S., Jaquet, V., Trabace, L., & Krause, K.-H. (2013). Severe life stress and oxidative stress in the brain: From animal models to human pathology. Antioxidants & Redox Signaling, 18(12), 1475–1490. Scholar
  125. Schieber, M., & Chandel, Navdeep S. (2014). ROS function in redox signaling and oxidative stress. Current Biology, 24(10), R453–R462. Scholar
  126. Seeman, T. E., McEwen, B. S., Rowe, J. W., & Singer, B. H. (2001). Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging. Proceedings of the National Academy of Sciences, 98(8), 4770–4775. Scholar
  127. Silverman, M. N., & Deuster, P. A. (2014). Biological mechanisms underlying the role of physical fitness in health and resilience. Interface focus, 4(5), 20140040.CrossRefGoogle Scholar
  128. Simpson, R. J., Lowder, T. W., Spielmann, G., Bigley, A. B., LaVoy, E. C., & Kunz, H. (2012). Exercise and the aging immune system. Ageing Research Reviews, 11(3), 404–420. Scholar
  129. Sommershof, A., Aichinger, H., Engler, H., Adenauer, H., Catani, C., Boneberg, E. M., et al. (2009). Substantial reduction in naïve and regulatory t cells following traumatic stress. Brain, Behavior, and Immunity, 23(8), 1117–1124. Scholar
  130. Song, C., Horrobin, D. F., & Leonard, B. E. (2006). The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats. Pharmacopsychiatry, 39(3), 88–99. Scholar
  131. Sousa, A. C. P. d. A., Marchand, A., Garcia, A., Gomez, J. F., Ylli, A., Guralnik, J. M., … Guerra, R. O. (2017). Cortisol and physical performance in older populations: Findings from the international mobility in aging study (IMIAS). Archives of Gerontology and Geriatrics, 71(Supplement C), 50–58. Scholar
  132. Southwick, S., & Charney, D. (2012). The science of resilience: Implications for the prevention and treatment of depression. Science, 338(5), 79–81.CrossRefGoogle Scholar
  133. Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M., & Pederson, B. K. (2003). Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α production in humans. The FASEB Journal. Scholar
  134. Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., et al. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. Journal of Physiology, 558(1), 263–275. Scholar
  135. Taksler, G. B., Cutler, D. M., Giovannucci, E., & Keating, N. L. (2015). Vitamin D deficiency in minority populations. Public health nutrition, 18(3), 379–391.CrossRefGoogle Scholar
  136. Tortosa-Martínez, J., Clow, A., Caus-Pertegaz, N., González-Caballero, G., Abellán-Miralles, I., & Saenz, M. J. (2015). Exercise increases the dynamics of diurnal cortisol secretion and executive function in people with amnestic mild cognitive impairment. Journal of Aging and Physical Activity, 23(4), 550–558.CrossRefGoogle Scholar
  137. Turan, B., Sims, T., Best, S. E., & Carstensen, L. L. (2016). Older age may offset genetic influence on affect: The COMT polymorphism and affective well-being across the life span. Psychology and Aging, 31(3), 287–294. Scholar
  138. van Beek, A. A., Sovran, B., Hugenholtz, F., Meijer, B., Hoogerland, J. A., Mihailova, V., et al. (2016). Supplementation with lactobacillus plantarum WCFS1 prevents decline of mucus barrier in colon of accelerated aging Ercc1-/Δ7 mice. Frontiers in Immunology, 7(OCT), 1–14. Scholar
  139. Veldhuis, J. D., Sharma, A., & Roelfsema, F. (2013). Age-dependent and gender-dependent regulation of hypothalamic-adrenocorticotropic-adrenal axis. Endocrinology and Metabolism Clinics, 42(2), 201–225. Scholar
  140. Vieira, V. J., Hu, L., Valentine, R. J., McAuley, E., Evans, E. M., Baynard, T., et al. (2009). Reduction in trunk fat predicts cardiovascular exercise training-related reductions in C-reactive protein. Brain, Behavior, and Immunity, 23(4), 485–491. Scholar
  141. Vilela, T. C., Muller, A. P., Damiani, A. P., Macan, T. P., da Silva, S., Canteiro, P. B., et al. (2017). Strength and aerobic exercises improve spatial memory in aging rats through stimulating distinct neuroplasticity mechanisms. Molecular Neurobiology, 54(10), 7928–7937. Scholar
  142. Von Linstow, C. U., Severino, M., Metaxas, A., Waider, J., Babcock, A. A., Lesch, K. P., et al. (2017). Effect of aging and Alzheimer’s disease-like pathology on brain monoamines in mice. Neurochemistry International, 108, 238–245. Scholar
  143. Walston, J., Xue, Q., Semba, R. D., Ferrucci, L., Cappola, A. R., Ricks, M., et al. (2006). Serum antioxidants, inflammation, and total mortality in older women. American Journal of Epidemiology, 163(1), 18–26. Scholar
  144. Wang, T., Cai, G., Qiu, Y., Fei, N., Zhang, M., Pang, X., et al. (2012). Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME Journal, 6(2), 320–329. Scholar
  145. Ward, D. D., Andel, R., Saunders, N. L., Thow, M. E., Klekociuk, S. Z., Bindoff, A. D., et al. (2017). The BDNF Val66Met polymorphism moderates the effect of cognitive reserve on 36-month cognitive change in healthy older adults. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 3(3), 323–331. Scholar
  146. Weaver, C. M., Alexander, D. D., Boushey, C. J., Dawson-Hughes, B., Lappe, J. M., LeBoff, M. S., et al. (2016). Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation. Osteoporosis International, 27(1), 367–376. Scholar
  147. Wellen, K. E., & Thompson, C. B. (2010). Cellular metabolic stress: Considering how cells respond to nutrient excess. Molecular Cell, 40(2), 323–332. Scholar
  148. Wilson, J. X. (2009). Mechanism of action of vitamin c in sepsis: Ascorbate modulates redox signaling in endothelium. BioFactors, 35(1), 5–13. Scholar
  149. Wood, S. K., Wood, C. S., Lombard, C. M., Lee, C. S., Zhang, Y., Finnell, J. E., et al. (2015). Inflammatory factors mediate vulnerability to a social stress- induced depressive-like phenotype in passive coping rats. Biological Psychiatry, 78(1), 38–48. Scholar
  150. Woods, J. A., Wilund, K. R., Martin, S. A., & Kistler, B. M. (2012). Exercise, inflammation and aging. Aging and Disease, 3(1), 130.PubMedGoogle Scholar
  151. Xia, S., Zhang, X., Zheng, S., Khanabdali, R., Kalionis, B., Wu, J., … Tai, X. (2016). An update on inflamm-aging: Mechanisms, prevention, and treatment. Journal of Immunology Research. Scholar
  152. Yang, C., Shirayama, Y., Zhang, J. C., Ren, Q., & Hashimoto, K. (2015). Peripheral interleukin-6 promotes resilience versus susceptibility to inescapable electric stress. Acta Neuropsychiatry, 27(5), 312–316. Scholar
  153. Zapata, H. J., & Quagliarello, V. J. (2015). The microbiota and microbiome in aging: Potential implications in health and age-related diseases. Journal of the American Geriatrics Society, 63(4), 776–781. Scholar
  154. Zschucke, E., Renneberg, B., Dimeo, F., Wüstenberg, T., & Ströhle, A. (2015). The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback. Psychoneuroendocrinology, 51, 414–425. Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.University of Maryland School of NursingBaltimoreUSA

Personalised recommendations