Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

The brain and immune system prompt energy shortage in chronic inflammation and ageing

Nature Reviews Rheumatology volume 13, pages 743–751 (2017)Cite this article

Subjects

Abstract

Sequelae frequently seen in patients with chronic inflammatory diseases, such as fatigue, depressed mood, sleep alterations, loss of appetite, muscle wasting, cachectic obesity, bone loss and hypertension, can be the result of energy shortages caused by an overactive immune system. These sequelae can also be found in patients with chronic inflammatory diseases that are in remission and in ageing individuals, despite the immune system being less active in these situations. This Perspectives article proposes a new way of understanding situations of chronic inflammation (such as rheumatic diseases) and ageing based on the principles of evolutionary medicine, energy regulation and neuroendocrine–immune crosstalk. A conceptual framework is provided to enable physicians and scientists to better understand the signs and symptoms of chronic inflammatory diseases and long-term disease consequences resulting from physical and mental inactivity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regulation of energy storage and energy release.
Figure 2: Average total energy expenditure for adults under various conditions.
Figure 3: The adaptive and maladaptive energy matrices.

Similar content being viewed by others

References

  1. Straub, R. H., Cutolo, M., Buttgereit, F. & Pongratz, G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J. Intern. Med. 267, 543–560 (2010).

    CAS  PubMed  Google Scholar 

  2. van de Laar, M. A., Nieuwenhuis, J. M., Former-Boon, M., Hulsing, J. & van der Korst, J. K. Nutritional habits of patients suffering from seropositive rheumatoid arthritis: a screening of 93 Dutch patients. Clin. Rheumatol. 9, 483–488 (1990).

    CAS  PubMed  Google Scholar 

  3. Lundberg, A. C., Akesson, A. & Akesson, B. Dietary intake and nutritional status in patients with systemic sclerosis. Ann. Rheum. Dis. 51, 1143–1148 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Chapman, I. M. The anorexia of aging. Clin. Geriatr. Med. 23, 735–756 (2007).

    PubMed  Google Scholar 

  5. Dantzer, R. & Kelley, K. W. Twenty years of research on cytokine-induced sickness behavior. Brain Behav. Immun. 21, 153–160 (2007).

    CAS  PubMed  Google Scholar 

  6. Olivieri, F. et al. MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res. Rev. 12, 1056–1068 (2013).

    CAS  PubMed  Google Scholar 

  7. Weyand, C. M. & Goronzy, J. J. Premature immunosenescence in rheumatoid arthritis. J. Rheumatol. 29, 1141–1146 (2002).

    PubMed  Google Scholar 

  8. Straub, R. H., Schölmerich, J. & Cutolo, M. The multiple facets of premature aging in rheumatoid arthritis. Arthritis Rheum. 48, 2713–2721 (2003).

    PubMed  Google Scholar 

  9. Roubenoff, R. et al. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J. Clin. Invest. 93, 2379–2386 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Baarends, E. M., Schols, A. M., Pannemans, D. L., Westerterp, K. R. & Wouters, E. F. Total free living energy expenditure in patients with severe chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 155, 549–554 (1997).

    CAS  PubMed  Google Scholar 

  11. Piche, T. et al. Resting energy expenditure in chronic hepatitis C. J. Hepatol. 33, 623–627 (2000).

    CAS  PubMed  Google Scholar 

  12. Kuhnke, A., Burmester, G. R., Krauss, S. & Buttgereit, F. Bioenergetics of immune cells to assess rheumatic disease activity and efficacy of glucocorticoid treatment. Ann. Rheum. Dis. 62, 133–139 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Tsigos, C. et al. Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. Neuroendocrinology 66, 54–62 (1997).

    CAS  PubMed  Google Scholar 

  14. Michaeli, B. et al. Effects of endotoxin on lactate metabolism in humans. Crit. Care 16, R139 (2012).

    PubMed  PubMed Central  Google Scholar 

  15. Straub, R. H. & Schradin, C. Chronic inflammatory systemic diseases: an evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health. 2016, 37–51 (2016).

    PubMed  PubMed Central  Google Scholar 

  16. Ghesquière, B., Wong, B. W., Kuchnio, A. & Carmeliet, P. Metabolism of stromal and immune cells in health and disease. Nature 511, 167–176 (2014).

    PubMed  Google Scholar 

  17. O'Neill, L. A. & Hardie, D. G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346–355 (2013).

    CAS  PubMed  Google Scholar 

  18. Krauss, S., Brand, M. D. & Buttgereit, F. Signaling takes a breath — new quantitative perspectives on bioenergetics and signal transduction. Immunity 15, 497–502 (2001).

    CAS  PubMed  Google Scholar 

  19. Weyand, C. M. & Goronzy, J. J. Immunometabolism in early and late stages of rheumatoid arthritis. Nat. Rev. Rheumatol. 13, 291–301 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Schäffler, A. & Schölmerich, J. Innate immunity and adipose tissue biology. Trends Immunol. 31, 228–235 (2010).

    PubMed  Google Scholar 

  21. Cannon, W. B. The wisdom of the body (Norton & Company, 1939).

    Google Scholar 

  22. Kotz, C. M. Integration of feeding and spontaneous physical activity: role for orexin. Physiol. Behav. 88, 294–301 (2006).

    CAS  PubMed  Google Scholar 

  23. Gluckman, P., Beedle, A. & Hanson, M. Principles of evolutionary medicine (Oxford Univ. Press, 2009).

    Google Scholar 

  24. Stearns, S. C. & Medzhitov, R. Evolutionary medicine (Sinauer Associates, 2016).

    Google Scholar 

  25. Blaxter, K. Energy metabolism in animals and man (Cambridge Univ. Press, 1989).

    Google Scholar 

  26. Prigogine, I. Time, structure, and fluctuations. Science 201, 777–785 (1978).

    CAS  PubMed  Google Scholar 

  27. Ruud, J., Steculorum, S. M. & Bruning, J. C. Neuronal control of peripheral insulin sensitivity and glucose metabolism. Nat. Commun. 8, 15259 (2017).

    PubMed  PubMed Central  Google Scholar 

  28. Hotamisligil, G. S. Inflammatory pathways and insulin action. Int. J. Obes. Relat. Metab. Disord. 27, S53–S55 (2003).

    CAS  PubMed  Google Scholar 

  29. Straub, R. H. Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases. Arthritis Res. Ther. 16, S4 (2014).

    PubMed  PubMed Central  Google Scholar 

  30. Takeda, S. & Karsenty, G. Molecular bases of the sympathetic regulation of bone mass. Bone 42, 837–840 (2008).

    CAS  PubMed  Google Scholar 

  31. Mbalaviele, G., Novack, D. V., Schett, G. & Teitelbaum, S. L. Inflammatory osteolysis: a conspiracy against bone. J. Clin. Invest. 127, 2030–2039 (2017).

    PubMed  PubMed Central  Google Scholar 

  32. Straub, R. H., Cutolo, M. & Pacifici, M. Evolutionary medicine and bone loss in chronic inflammatory diseases — a theory of inflammation-related osteopenia. Semin. Arthritis Rheum. 45, 220–228 (2015).

    PubMed  PubMed Central  Google Scholar 

  33. Peters, A. et al. The selfish brain: competition for energy resources. Neurosci. Biobehav. Rev. 28, 143–180 (2004).

    CAS  PubMed  Google Scholar 

  34. Matarese, G. & La Cava, A. The intricate interface between immune system and metabolism. Trends Immunol. 25, 193–200 (2004).

    CAS  PubMed  Google Scholar 

  35. Frauwirth, K. A. & Thompson, C. B. Regulation of T lymphocyte metabolism. J. Immunol. 172, 4661–4665 (2004).

    CAS  PubMed  Google Scholar 

  36. Spies, C. M., Straub, R. H. & Buttgereit, F. Energy metabolism and rheumatic diseases: from cell to organism. Arthritis Res. Ther. 14, 216–225 (2012).

    PubMed  PubMed Central  Google Scholar 

  37. Bajgar, A. et al. Extracellular adenosine mediates a systemic metabolic switch during immune response. PLoS Biol. 13, e1002135 (2015).

    PubMed  PubMed Central  Google Scholar 

  38. Straub, R. H. Evolutionary medicine and chronic inflammatory state — known and new concepts in pathophysiology. J. Mol. Med. (Berl.) 90, 523–534 (2012).

    Google Scholar 

  39. Toth, M. J., Gottlieb, S. S., Fisher, M. L. & Poehlman, E. T. Daily energy requirements in heart failure patients. Metabolism 46, 1294–1298 (1997).

    CAS  PubMed  Google Scholar 

  40. Wang, A. Y. Energy intake and energy expenditure profiles in peritoneal dialysis patients. J. Ren Nutr. 21, 31–34 (2011).

    PubMed  Google Scholar 

  41. Nairne, J. S. & Pandeirada, J. N. Adaptive memory: ancestral priorities and the mnemonic value of survival processing. Cogn. Psychol. 61, 1–22 (2010).

    PubMed  Google Scholar 

  42. Yamauchi, T. & Sato, H. Nutritional status, activity pattern, and dietary intake among the Baka hunter-gatherers in the village camps in Cameroon. Afr. Study Monogr. 21, 67–82 (2000).

    Google Scholar 

  43. Boyer, D. & Walsh, P. D. Modelling the mobility of living organisms in heterogeneous landscapes: does memory improve foraging success? Philos. Trans. A Math. Phys. Eng. Sci. 368, 5645–5659 (2010).

    PubMed  Google Scholar 

  44. Murphy, K. M., Travers, P. & Walport, M. Janeway's Immunobiology (Taylor & Francis, 2011).

    Google Scholar 

  45. Buttgereit, F., Burmester, G. R. & Brand, M. D. Bioenergetics of immune functions: fundamental and therapeutic aspects. Immunol. Today 21, 192–199 (2000).

    CAS  PubMed  Google Scholar 

  46. Besedovsky, H. O. & del Rey, A. Immune-neuro-endocrine interactions: facts and hypotheses. Endocr. Rev. 17, 64–102 (1996).

    CAS  PubMed  Google Scholar 

  47. Simonds, S. E. et al. Leptin mediates the increase in blood pressure associated with obesity. Cell 159, 1404–1416 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Abella, V. et al. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat. Rev. Rheumatol. 13, 100–109 (2017).

    CAS  PubMed  Google Scholar 

  49. Bartness, T. J., Liu, Y., Shrestha, Y. B. & Ryu, V. Neural innervation of white adipose tissue and the control of lipolysis. Front. Neuroendocrinol. 35, 473–493 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang, H. J., Zucker, I. H. & Wang, W. Muscle reflex in heart failure: the role of exercise training. Front. Physiol. 3, 398 (2012).

    PubMed  PubMed Central  Google Scholar 

  51. Rubin, R. T., Rhodes, M. E. & Czambel, R. K. Plasma leptin suppression by arginine vasopressin in normal women and men. Life Sci. 72, 1209–1220 (2003).

    CAS  PubMed  Google Scholar 

  52. Pedersen, B. K. Muscle as a secretory organ. Compr. Physiol. 3, 1337–1362 (2013).

    PubMed  Google Scholar 

  53. Path, G. et al. Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by β-adrenergic activation and effects of IL-6 on adipocyte function. J. Clin. Endocrinol. Metab. 86, 2281–2288 (2001).

    CAS  PubMed  Google Scholar 

  54. Petersen, E. W. et al. Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. Am. J. Physiol. Endocrinol. Metab. 288, E155–E162 (2005).

    CAS  PubMed  Google Scholar 

  55. Chu, C. A. et al. Effects of free fatty acids on hepatic glycogenolysis and gluconeogenesis in conscious dogs. Am. J. Physiol. Endocrinol. Metab. 282, E402–E411 (2002).

    CAS  PubMed  Google Scholar 

  56. Princiotta, M. F. et al. Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18, 343–354 (2003).

    CAS  PubMed  Google Scholar 

  57. Torine, I. J., Denne, S. C., Wright-Coltart, S. & Leitch, C. Effect of late-onset sepsis on energy expenditure in extremely premature infants. Pediatr. Res. 61, 600–603 (2007).

    PubMed  Google Scholar 

  58. Straub, R. H. et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J. Clin. Endocrinol. Metab. 83, 2012–2017 (1998).

    CAS  PubMed  Google Scholar 

  59. Lutgendorf, S. K. et al. Life stress, mood disturbance, and elevated interleukin-6 in healthy older women. J. Gerontol. A Biol. Sci. Med. Sci. 54, M434–M439 (1999).

    CAS  PubMed  Google Scholar 

  60. Straub, R. H. et al. Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion. Arthritis Rheum. 48, 1504–1512 (2003).

    CAS  PubMed  Google Scholar 

  61. Caliyurt, O. & Altiay, G. Resting energy expenditure in manic episode. Bipolar Disord. 11, 102–106 (2009).

    PubMed  Google Scholar 

  62. Faurholt-Jepsen, M., Brage, S., Vinberg, M. & Kessing, L. V. State-related differences in the level of psychomotor activity in patients with bipolar disorder — continuous heart rate and movement monitoring. Psychiatry Res. 237, 166–174 (2016).

    PubMed  PubMed Central  Google Scholar 

  63. Gaba, A. M. et al. Energy balance in early-stage Huntington disease. Am. J. Clin. Nutr. 81, 1335–1341 (2005).

    CAS  PubMed  Google Scholar 

  64. Gonseth, S. et al. Association between smoking and total energy expenditure in a multi-country study. Nutr. Metab. (Lond.) 11, 48–11 (2014).

    Google Scholar 

  65. Wong, J. A. & Leventhal, A. M. Smoking-related correlates of psychomotor restlessness and agitation in a community sample of daily cigarette smokers. Am. J. Addict. 24, 166–172 (2015).

    PubMed  PubMed Central  Google Scholar 

  66. Holland-Fischer, P. et al. Increased energy expenditure and glucose oxidation during acute nontraumatic skin pain in humans. Eur. J. Anaesthesiol. 26, 311–317 (2009).

    PubMed  Google Scholar 

  67. Greisen, J. et al. Acute pain induces insulin resistance in humans. Anesthesiology 95, 578–584 (2001).

    CAS  PubMed  Google Scholar 

  68. Xu, Z., Li, Y., Wang, J. & Li, J. Effect of postoperative analgesia on energy metabolism and role of cyclooxygenase-2 inhibitors for postoperative pain management after abdominal surgery in adults. Clin. J. Pain 29, 570–576 (2013).

    PubMed  Google Scholar 

  69. Hitze, B. et al. How the selfish brain organizes its supply and demand. Front. Neuroenergetics 2, 7–17 (2010).

    PubMed  PubMed Central  Google Scholar 

  70. Yokozeki, T. et al. Work intensity during working hours and different types of care done by special nursing home workers [Japanese]. Nihon Eiseigaku Zasshi 52, 567–573 (1997).

    CAS  PubMed  Google Scholar 

  71. Ravussin, E., Lillioja, S., Anderson, T. E., Christin, L. & Bogardus, C. Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber. J. Clin. Invest. 78, 1568–1578 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Markwald, R. R. et al. Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain. Proc. Natl Acad. Sci. USA 110, 5695–5700 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Jung, C. M. et al. Energy expenditure during sleep, sleep deprivation and sleep following sleep deprivation in adult humans. J. Physiol. 589, 235–244 (2011).

    CAS  PubMed  Google Scholar 

  74. Fekete, K. et al. Resting energy expenditure in OSAS: the impact of a single CPAP application. Sleep Breath. 20, 121–128 (2016).

    PubMed  Google Scholar 

  75. Schmidt, W. D., O'Connor, P. J., Cochrane, J. B. & Cantwell, M. Resting metabolic rate is influenced by anxiety in college men. J. Appl. Physiol. (1985) 80, 638–642 (1996).

    CAS  Google Scholar 

  76. Cannon, W. B. Bodily changes in pain, hunger, fear, and rage (D. Appleton and Company, 1927).

    Google Scholar 

  77. Speakman, J. R. & Westerterp, K. R. Associations between energy demands, physical activity, and body composition in adult humans between 18 and 96 y of age. Am. J. Clin. Nutr. 92, 826–834 (2010).

    CAS  PubMed  Google Scholar 

  78. Munsterman, T., Takken, T. & Wittink, H. Are persons with rheumatoid arthritis deconditioned? A review of physical activity and aerobic capacity. BMC. Musculoskelet. Disord. 13, 202–213 (2012).

    PubMed  PubMed Central  Google Scholar 

  79. Roubenoff, R. et al. Low physical activity reduces total energy expenditure in women with rheumatoid arthritis: implications for dietary intake recommendations. Am. J. Clin. Nutr. 76, 774–779 (2002).

    CAS  PubMed  Google Scholar 

  80. Gualano, B., Bonfa, E., Pereira, R. M. R. & Silva, C. A. Physical activity for paediatric rheumatic diseases: standing up against old paradigms. Nat. Rev. Rheumatol. 13, 368–379 (2017).

    PubMed  Google Scholar 

  81. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376–381 (2014).

    CAS  PubMed  Google Scholar 

  82. LaFleur, C. et al. HLA-DR antigen frequencies in Mexican patients with dengue virus infection: HLA-DR4 as a possible genetic resistance factor for dengue hemorrhagic fever. Hum. Immunol. 63, 1039–1044 (2002).

    CAS  PubMed  Google Scholar 

  83. Williams, G. C. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11, 398–411 (1957).

    Google Scholar 

  84. Alves, A. J. et al. Physical activity in primary and secondary prevention of cardiovascular disease: overview updated. World J. Cardiol. 8, 575–583 (2016).

    PubMed  PubMed Central  Google Scholar 

  85. Chang, Y. K., Chu, C. H., Chen, F. T., Hung, T. M. & Etnier, J. L. Combined effects of physical activity and obesity on cognitive function: independent, overlapping, moderator, and mediator models. Sports Med. 47, 449–468 (2017).

    PubMed  Google Scholar 

  86. Paley, C. A. & Johnson, M. I. Physical activity to reduce systemic inflammation associated with chronic pain and obesity: a narrative review. Clin. J. Pain 32, 365–370 (2016).

    PubMed  Google Scholar 

  87. Phillips, C., Baktir, M. A., Srivatsan, M. & Salehi, A. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front. Cell. Neurosci. 8, 170 (2014).

    PubMed  PubMed Central  Google Scholar 

  88. Phillips, C., Baktir, M. A., Das, D., Lin, B. & Salehi, A. The link between physical activity and cognitive dysfunction in Alzheimer disease. Phys. Ther. 95, 1046–1060 (2015).

    PubMed  Google Scholar 

  89. Hallgren, M. et al. Exercise, physical activity, and sedentary behavior in the treatment of depression: broadening the scientific perspectives and clinical opportunities. Front. Psychiatry. 7, 36 (2016).

    PubMed  PubMed Central  Google Scholar 

  90. McPhee, J. S. et al. Physical activity in older age: perspectives for healthy ageing and frailty. Biogerontology 17, 567–580 (2016).

    PubMed  PubMed Central  Google Scholar 

  91. Kyu, H. H. et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ 354, i3857 (2016).

    PubMed  PubMed Central  Google Scholar 

  92. Buttgereit, F., Burmester, G. R., Straub, R. H., Seibel, M. J. & Zhou, H. Exogenous and endogenous glucocorticoids in rheumatic diseases. Arthritis Rheum. 63, 1–9 (2011).

    CAS  PubMed  Google Scholar 

  93. Hiroyama, M. et al. Altered lipid metabolism in vasopressin V1B receptor-deficient mice. Eur. J. Pharmacol. 602, 455–461 (2009).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

R.H.S. would like to thank David Pisetsky of Duke University Medical Center, Durham, North Carolina, USA, who reviewed an early version of the manuscript and provided helpful editorial comments, and the team of Martin Fleck at University Hospital Regensburg, Regensburg, Germany, for discussing the clinical aspects of the present work during a seminar in 2016. The work of R.H.S. is supported financially by the Deutsche Forschungsgemeinschaft (DFG), the German Federal Ministry of Education and Research and the State of Bavaria (through local funding by University Hospital Regensburg).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg, Franz Josef Strauß Allee 11, Regensburg, 93053, Germany

    Rainer H. Straub

Authors
  1. Rainer H. Straub
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rainer H. Straub.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Supplementary information

Supplementary information S1 (table)

Adaptive programmes in chronic inflammatory diseases and during ageing that protect against energy shortages (PDF 72 kb)

PowerPoint slides

Glossary

Context-associated anorexia

Anorexia that is dependent on a particular circumstance, such as sickness behaviour during an infection, mental activation in bipolar disorder or age-related anorexia.

Insulin resistance

A condition of low insulin sensitivity with marked changes to the insulin receptor and to downstream signalling pathways; because insulin is responsible for the storage of glucose and free fatty acids, a lower insulin sensitivity leads to reduced energy storage and increased levels of energy-rich fuels in the circulation.

Pro-inflammatory load

A high level of systemic activity in the immune system, as measured by an increased erythrocyte sedimentation rate, or increased levels of serum C-reactive protein or serum IL-6.

Psychomotor activity

Activity induced by the brain that leads to activation of the skeletal muscles and the heart.

Super-systems

Integrative systems at the top level of homeostatic regulation of the body; examples include the nervous, endocrine and immune systems.

Thermodynamically open system

Systems, such as the human body, that can take up and lose energy, mainly in the form of heat.

State and trait anxiety

State anxiety is how a person is feeling at the time of a perceived threat, whereas trait anxiety is the enduring disposition to feel stress, worry and discomfort.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Straub, R. The brain and immune system prompt energy shortage in chronic inflammation and ageing. Nat Rev Rheumatol 13, 743–751 (2017). https://doi.org/10.1038/nrrheum.2017.172

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2017.172

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing