pp 1–12 | Cite as

Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases

  • Priya Balasubramanian
  • Delton Hall
  • Madhan SubramanianEmail author
Review Article


Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.


Obesity Aging Hypertension Sympathetic nerve activity Inflammation Leptin Renin-angiotensin system Oxidative stress Cellular senescence 


Funding information

This work was supported by RAC fund to MS from the Center for Veterinary Health Sciences, Oklahoma State University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Aizawa-Abe M, Ogawa Y, Masuzaki H, Ebihara K, Satoh N, Iwai H, Matsuoka N, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Nakao K (2000) Pathophysiological role of leptin in obesity-related hypertension. J Clin Invest 105(9):1243–1252CrossRefPubMedCentralPubMedGoogle Scholar
  2. AlGhatrif M, Strait JB, Morrell CH, Canepa M, Wright J, Elango P, Scuteri A, Najjar SS, Ferrucci L, Lakatta EG (2013) Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore Longitudinal Study of Aging. Hypertension 62(5):934–941CrossRefPubMedGoogle Scholar
  3. Bailey-Downs LC, Tucsek Z, Toth P, Sosnowska D, Gautam T, Sonntag WE, Csiszar A, Ungvari Z (2013) Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation. J Gerontol A Biol Sci Med Sci 68(7):780–792CrossRefPubMedGoogle Scholar
  4. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236CrossRefPubMedCentralPubMedGoogle Scholar
  5. Balasko M, Soos S, Szekely M, Petervari E (2014) Leptin and aging: review and questions with particular emphasis on its role in the central regulation of energy balance. J Chem Neuroanat 61-62:248–255CrossRefPubMedGoogle Scholar
  6. Balivada S, Ganta CK, Zhang Y, Pawar HN, Ortiz RJ, Becker KG, Khan AM, Kenney MJ (2017) Microarray analysis of aging-associated immune system alterations in the rostral ventrolateral medulla of F344 rats. Physiol Genomics 49(8):400–415CrossRefPubMedCentralPubMedGoogle Scholar
  7. Barnes MJ, McDougal DH (2014) Leptin into the rostral ventral lateral medulla (RVLM) augments renal sympathetic nerve activity and blood pressure. Front Neurosci 8:232PubMedPubMedCentralGoogle Scholar
  8. Bhat R, Crowe EP, Bitto A, Moh M, Katsetos CD, Garcia FU, Johnson FB, Trojanowski JQ, Sell C, Torres C (2012) Astrocyte senescence as a component of Alzheimer’s disease. PLoS One 7(9):e45069CrossRefPubMedCentralPubMedGoogle Scholar
  9. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL, Investigators SH (2014) A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370(15):1393–1401CrossRefPubMedGoogle Scholar
  10. Buckman LB, Thompson MM, Moreno HN, Ellacott KL (2013) Regional astrogliosis in the mouse hypothalamus in response to obesity. J Comp Neurol 521(6):1322–1333CrossRefPubMedCentralPubMedGoogle Scholar
  11. Chinta SJ, Woods G, Rane A, Demaria M, Campisi J, Andersen JK (2015) Cellular senescence and the aging brain. Exp Gerontol 68:3–7CrossRefPubMedGoogle Scholar
  12. Chinta SJ, Woods G, Demaria M, Rane A, Zou Y, McQuade A, Rajagopalan S, Limbad C, Madden DT, Campisi J, Andersen JK (2018) Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to Parkinson’s disease. Cell Rep 22(4):930–940CrossRefPubMedCentralPubMedGoogle Scholar
  13. Correia ML, Haynes WG, Rahmouni K, Morgan DA, Sivitz WI, Mark AL (2002) The concept of selective leptin resistance: evidence from agouti yellow obese mice. Diabetes 51(2):439–442CrossRefPubMedGoogle Scholar
  14. Csipo T, Fulop GA, Lipecz A, Tarantini S, Kiss T, Balasubramanian P, Csiszar A, Ungvari Z, Yabluchanskiy A (2018) Short-term weight loss reverses obesity-induced microvascular endothelial dysfunction. GeroscienceGoogle Scholar
  15. Dampney RA (1994) Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74(2):323–364CrossRefPubMedGoogle Scholar
  16. de Beus E, de Jager RL, Beeftink MM, Sanders MF, Spiering W, Vonken EJ, Voskuil M, Bots ML, Blankestijn PJ, S. s. group (2017) Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension. J Clin Hypertens (Greenwich) 19(11):1125–1133CrossRefGoogle Scholar
  17. de Kloet AD, Pati D, Wang L, Hiller H, Sumners C, Frazier CJ, Seeley RJ, Herman JP, Woods SC, Krause EG (2013) Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus protect against diet-induced obesity. J Neurosci 33(11):4825–4833CrossRefPubMedCentralPubMedGoogle Scholar
  18. de Kloet AD, Pioquinto DJ, Nguyen D, Wang L, Smith JA, Hiller H, Sumners C (2014) Obesity induces neuroinflammation mediated by altered expression of the renin-angiotensin system in mouse forebrain nuclei. Physiol Behav 136:31–38CrossRefPubMedGoogle Scholar
  19. de Souza SB, Rocha JA, Cuoco MA, Guerra GM, Ferreira-Filho JC, Borile S, Krieger EM, Bortolotto LA, Consolim-Colombo FM (2013) High muscle sympathetic nerve activity is associated with left ventricular dysfunction in treated hypertensive patients. Am J Hypertens 26(7):912–917CrossRefPubMedGoogle Scholar
  20. Dinenno FA, Jones PP, Seals DR, Tanaka H (2000) Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol Heart Circ Physiol 278(4):H1205–H1210CrossRefPubMedGoogle Scholar
  21. Diz DI, Varagic J, Groban L (2008) Aging and the brain renin-angiotensin system: relevance to age-related decline in cardiac function. Futur Cardiol 4(3):237–245CrossRefGoogle Scholar
  22. do Carmo JM, da Silva AA, Cai Z, Lin S, Dubinion JH, Hall JE (2011) Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension 57(5):918–926CrossRefPubMedCentralPubMedGoogle Scholar
  23. do Carmo JM, da Silva AA, Wang Z, Fang T, Aberdein N, de Lara Rodriguez CE, Hall JE (2016) Obesity-induced hypertension: brain signaling pathways. Curr Hypertens Rep 18(7):58CrossRefPubMedCentralPubMedGoogle Scholar
  24. Ebert TJ, Morgan BJ, Barney JA, Denahan T, Smith JJ (1992) Effects of aging on baroreflex regulation of sympathetic activity in humans. Am J Phys 263(3 Pt 2):H798–H803Google Scholar
  25. Elffers TW, de Mutsert R, Lamb HJ, de Roos A, Willems van Dijk K, Rosendaal FR, Jukema JW, Trompet S (2017) Body fat distribution, in particular visceral fat, is associated with cardiometabolic risk factors in obese women. PLoS One 12(9):e0185403CrossRefPubMedCentralPubMedGoogle Scholar
  26. Engeli S, Sharma AM (2002) Emerging concepts in the pathophysiology and treatment of obesity-associated hypertension. Curr Opin Cardiol 17(4):355–359CrossRefPubMedGoogle Scholar
  27. Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E (2006) Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension 48(5):787–796CrossRefPubMedGoogle Scholar
  28. Esler M, Lambert G, Schlaich M, Dixon J, Sari CI, Lambert E (2018) Obesity paradox in hypertension: is this because sympathetic activation in obesity-hypertension takes a benign form? Hypertension 71(1):22–33CrossRefPubMedGoogle Scholar
  29. Fagius J, Berne C (1994) Increase in muscle nerve sympathetic activity in humans after food intake. Clin Sci (Lond) 86(2):159–167CrossRefGoogle Scholar
  30. Fisher JP, Young CN, Fadel PJ (2009) Central sympathetic overactivity: maladies and mechanisms. Auton Neurosci 148(1–2):5–15CrossRefPubMedCentralPubMedGoogle Scholar
  31. Forman JP, Stampfer MJ, Curhan GC (2009) Diet and lifestyle risk factors associated with incident hypertension in women. JAMA 302(4):401–411CrossRefPubMedCentralPubMedGoogle Scholar
  32. Franklin SS (1999) Ageing and hypertension: the assessment of blood pressure indices in predicting coronary heart disease. J Hypertens Suppl 17(5):S29–S36PubMedPubMedCentralGoogle Scholar
  33. Gabriely I, Ma XH, Yang XM, Rossetti L, Barzilai N (2002) Leptin resistance during aging is independent of fat mass. Diabetes 51(4):1016–1021CrossRefPubMedGoogle Scholar
  34. Gao L, Zimmerman MC, Biswal S, Zucker IH (2017) Selective Nrf2 gene deletion in the rostral ventrolateral medulla evokes hypertension and sympathoexcitation in mice. Hypertension 69(6):1198–1206CrossRefPubMedCentralPubMedGoogle Scholar
  35. Grassi G, Seravalle G, Dell'Oro R, Turri C, Bolla GB, Mancia G (2000) Adrenergic and reflex abnormalities in obesity-related hypertension. Hypertension 36(4):538–542CrossRefPubMedCentralPubMedGoogle Scholar
  36. Grassi G, Quarti-Trevano F, Seravalle G, Arenare F, Volpe M, Furiani S, Dell'Oro R, Mancia G (2011) Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension 57(4):846–851CrossRefPubMedCentralPubMedGoogle Scholar
  37. Griggio MA, Richard D, Leblanc J (1992) Effects of fasting and food restriction on sympathetic activity in brown adipose tissue in mice. J Comp Physiol B 162(7):602–606CrossRefPubMedCentralPubMedGoogle Scholar
  38. Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7(5):335–346CrossRefPubMedCentralGoogle Scholar
  39. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME (2015) Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res 116(6):991–1006CrossRefPubMedCentralPubMedGoogle Scholar
  40. Head GA, Lim K, Barzel B, Burke SL, Davern PJ (2014) Central nervous system dysfunction in obesity-induced hypertension. Curr Hypertens Rep 16(9):466CrossRefPubMedGoogle Scholar
  41. Hijmering ML, Stroes ES, Olijhoek J, Hutten BA, Blankestijn PJ, Rabelink TJ (2002) Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J Am Coll Cardiol 39(4):683–688CrossRefPubMedGoogle Scholar
  42. Hsuchou H, He Y, Kastin AJ, Tu H, Markadakis EN, Rogers RC, Fossier PB, Pan W (2009) Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain 132(Pt 4):889–902PubMedPubMedCentralGoogle Scholar
  43. Huang Z, Willett WC, Manson JE, Rosner B, Stampfer MJ, Speizer FE, Colditz GA (1998) Body weight, weight change, and risk for hypertension in women. Ann Intern Med 128(2):81–88CrossRefPubMedGoogle Scholar
  44. Indumathy J, Pal GK, Pal P, Ananthanarayanan PH, Parija SC, Balachander J, Dutta TK (2015) Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity. Metabolism 64(12):1704–1714CrossRefPubMedGoogle Scholar
  45. Jones PP, Davy KP, Alexander S, Seals DR (1997) Age-related increase in muscle sympathetic nerve activity is associated with abdominal adiposity. Am J Phys 272(6 Pt 1):E976–E980Google Scholar
  46. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT (2011) Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 365(20):1876–1885CrossRefPubMedGoogle Scholar
  47. Kaye D, Esler M (2005) Sympathetic neuronal regulation of the heart in aging and heart failure. Cardiovasc Res 66(2):256–264CrossRefPubMedGoogle Scholar
  48. Kishi T, Hirooka Y, Ogawa K, Konno S, Sunagawa K (2011) Calorie restriction inhibits sympathetic nerve activity via anti-oxidant effect in the rostral ventrolateral medulla of obesity-induced hypertensive rats. Clin Exp Hypertens 33(4):240–245CrossRefPubMedGoogle Scholar
  49. Koh H, Hayashi T, Sato KK, Harita N, Maeda I, Nishizawa Y, Endo G, Fujimoto WY, Boyko EJ, Hikita Y (2011) Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study. Hypertens Res 34(5):565–572CrossRefPubMedGoogle Scholar
  50. Konno S, Hirooka Y, Kishi T, Sunagawa K (2012) Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats. J Hypertens 30(10):1992–1999CrossRefPubMedGoogle Scholar
  51. Kotsis V, Stabouli S, Papakatsika S, Rizos Z, Parati G (2010) Mechanisms of obesity-induced hypertension. Hypertens Res 33(5):386–393CrossRefPubMedGoogle Scholar
  52. Kuo JJ, Jones OB, Hall JE (2001) Inhibition of NO synthesis enhances chronic cardiovascular and renal actions of leptin. Hypertension 37(2 Pt 2):670–676CrossRefPubMedGoogle Scholar
  53. Lambert E, Straznicky N, Schlaich M, Esler M, Dawood T, Hotchkin E, Lambert G (2007) Differing pattern of sympathoexcitation in normal-weight and obesity-related hypertension. Hypertension 50(5):862–868CrossRefPubMedGoogle Scholar
  54. Levelt E, Pavlides M, Banerjee R, Mahmod M, Kelly C, Sellwood J, Ariga R, Thomas S, Francis J, Rodgers C, Clarke W, Sabharwal N, Antoniades C, Schneider J, Robson M, Clarke K, Karamitsos T, Rider O, Neubauer S (2016) Ectopic and visceral fat deposition in lean and obese patients with type 2 diabetes. J Am Coll Cardiol 68(1):53–63CrossRefPubMedCentralPubMedGoogle Scholar
  55. Machleidt F, Simon P, Krapalis AF, Hallschmid M, Lehnert H, Sayk F (2013) Experimental hyperleptinemia acutely increases vasoconstrictory sympathetic nerve activity in healthy humans. J Clin Endocrinol Metab 98(3):E491–E496CrossRefPubMedGoogle Scholar
  56. Malpas SC (2010) Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev 90(2):513–557CrossRefPubMedGoogle Scholar
  57. Mark AL (2013) Selective leptin resistance revisited. Am J Physiol Regul Integr Comp Physiol 305(6):R566–R581CrossRefPubMedCentralPubMedGoogle Scholar
  58. Mark AL, Agassandian K, Morgan DA, Liu X, Cassell MD, Rahmouni K (2009) Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney. Hypertension 53(2):375–380CrossRefPubMedGoogle Scholar
  59. Marsh AJ, Fontes MA, Killinger S, Pawlak DB, Polson JW, Dampney RA (2003) Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus. Hypertension 42(4):488–493CrossRefPubMedGoogle Scholar
  60. Moreira MC, Pinto IS, Mourão AA, Fajemiroye JO, Colombari E, Reis Â, Freiria-Oliveira AH, Ferreira-Neto ML, Pedrino GR (2015) Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome? Front Physiol 6:234CrossRefPubMedCentralPubMedGoogle Scholar
  61. Nagae A, Fujita M, Kawarazaki H, Matsui H, Ando K, Fujita T (2009) Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in obesity-induced hypertension. Circulation 119(7):978–986CrossRefPubMedGoogle Scholar
  62. Ootsuka Y, Terui N (1997) Functionally different neurons are organized topographically in the rostral ventrolateral medulla of rabbits. J Auton Nerv Syst 67(1–2):67–78CrossRefPubMedGoogle Scholar
  63. Osborn JW, Kuroki MT (2012) Sympathetic signatures of cardiovascular disease: a blueprint for development of targeted sympathetic ablation therapies. Hypertension 59(3):545–547CrossRefPubMedCentralPubMedGoogle Scholar
  64. Palmer AK, Tchkonia T, LeBrasseur NK, Chini EN, Xu M, Kirkland JL (2015) Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes 64(7):2289–2298CrossRefPubMedCentralPubMedGoogle Scholar
  65. Perez LM, Pareja-Galeano H, Sanchis-Gomar F, Emanuele E, Lucia A, Galvez BG (2016) ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J Physiol 594(12):3187–3207CrossRefPubMedCentralPubMedGoogle Scholar
  66. Pfeifer MA, Weinberg CR, Cook D, Best JD, Reenan A, Halter JB (1983) Differential changes of autonomic nervous system function with age in man. Am J Med 75(2):249–258CrossRefPubMedGoogle Scholar
  67. Prior LJ, Eikelis N, Armitage JA, Davern PJ, Burke SL, Montani JP, Barzel B, Head GA (2010) Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 55(4):862–868CrossRefGoogle Scholar
  68. Purkayastha S, Zhang G, Cai D (2011) Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-beta and NF-kappaB. Nat Med 17(7):883–887CrossRefPubMedCentralPubMedGoogle Scholar
  69. Rabkin SW, Chen Y, Leiter L, Liu L, Reeder BA (1997) Risk factor correlates of body mass index. Canadian Heart Health Surveys Research Group. CMAJ 157(Suppl 1):S26–S31PubMedGoogle Scholar
  70. Rahmouni K, Morgan DA (2007) Hypothalamic arcuate nucleus mediates the sympathetic and arterial pressure responses to leptin. Hypertension 49(3):647–652CrossRefPubMedGoogle Scholar
  71. Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192(4):547–556CrossRefPubMedCentralPubMedGoogle Scholar
  72. Schafer MJ, White TA, Evans G, Tonne JM, Verzosa GC, Stout MB, Mazula DL, Palmer AK, Baker DJ, Jensen MD, Torbenson MS, Miller JD, Ikeda Y, Tchkonia T, van Deursen JM, Kirkland JL, LeBrasseur NK (2016) Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 65(6):1606–1615CrossRefPubMedCentralPubMedGoogle Scholar
  73. Seals DR, Bell C (2004) Chronic sympathetic activation: consequence and cause of age-associated obesity? Diabetes 53(2):276–284CrossRefPubMedGoogle Scholar
  74. Shek EW, Brands MW, Hall JE (1998) Chronic leptin infusion increases arterial pressure. Hypertension 31(1 Pt 2):409–414CrossRefPubMedGoogle Scholar
  75. Shirakawa K, Yan X, Shinmura K, Endo J, Kataoka M, Katsumata Y, Yamamoto T, Anzai A, Isobe S, Yoshida N, Itoh H, Manabe I, Sekai M, Hamazaki Y, Fukuda K, Minato N, Sano M (2016) Obesity accelerates T cell senescence in murine visceral adipose tissue. J Clin Invest 126(12):4626–4639CrossRefPubMedCentralPubMedGoogle Scholar
  76. Smith MM, Minson CT (2012) Obesity and adipokines: effects on sympathetic overactivity. J Physiol 590(8):1787–1801CrossRefPubMedCentralPubMedGoogle Scholar
  77. Stocker SD, Muntzel MS (2013) Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification. Am J Physiol Heart Circ Physiol 305(10):H1407–H1416CrossRefPubMedCentralPubMedGoogle Scholar
  78. Subramanian M, Mueller PJ (2016) Altered differential control of sympathetic outflow following sedentary conditions: role of subregional neuroplasticity in the RVLM. Front Physiol 7:290CrossRefPubMedCentralPubMedGoogle Scholar
  79. Tan FC, Hutchison ER, Eitan E, Mattson MP (2014) Are there roles for brain cell senescence in aging and neurodegenerative disorders? Biogerontology 15(6):643–660CrossRefPubMedCentralPubMedGoogle Scholar
  80. Tarantini S, Valcarcel-Ares MN, Yabluchanskiy A, Tucsek Z, Hertelendy P, Kiss T, Gautam T, Zhang XA, Sonntag WE, de Cabo R, Farkas E, Elliott MH, Kinter MT, Deak F, Ungvari Z, Csiszar A (2018) Nrf2 deficiency exacerbates obesity-induced oxidative stress, neurovascular dysfunction, blood-brain barrier disruption, neuroinflammation, amyloidogenic gene expression, and cognitive decline in mice, mimicking the aging phenotype. J Gerontol A Biol Sci Med Sci 73(7):853–863CrossRefPubMedGoogle Scholar
  81. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschop MH, Schwartz MW (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122(1):153–162CrossRefPubMedGoogle Scholar
  82. Tucsek Z, Toth P, Sosnowska D, Gautam T, Mitschelen M, Koller A, Szalai G, Sonntag WE, Ungvari Z, Csiszar A (2014a) Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 69(10):1212–1226CrossRefPubMedGoogle Scholar
  83. Tucsek Z, Toth P, Tarantini S, Sosnowska D, Gautam T, Warrington JP, Giles CB, Wren JD, Koller A, Ballabh P, Sonntag WE, Ungvari Z, Csiszar A (2014b) Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice. J Gerontol A Biol Sci Med Sci 69(11):1339–1352CrossRefPubMedCentralPubMedGoogle Scholar
  84. Ungvari Z, Bailey-Downs L, Gautam T, Jimenez R, Losonczy G, Zhang C, Ballabh P, Recchia FA, Wilkerson DC, Sonntag WE, Pearson K, de Cabo R, Csiszar A (2011) Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am J Physiol Heart Circ Physiol 300(4):H1133–H1140CrossRefPubMedCentralPubMedGoogle Scholar
  85. Valcarcel-Ares MN, Tucsek Z, Kiss T, Giles CB, Tarantini S, Yabluchanskiy A, Balasubramanian P, Gautam T, Galvan V, Ballabh P, Richardson A, Freeman WM, Wren JD, Deak F, Ungvari Z, Csiszar A (2018) Obesity in aging exacerbates Neuroinflammation, dysregulating synaptic function-related genes and altering eicosanoid synthesis in the mouse hippocampus: potential role in impaired synaptic plasticity and cognitive decline. J Gerontol A Biol Sci Med SciGoogle Scholar
  86. van Deursen JM (2014) The role of senescent cells in ageing. Nature 509(7501):439–446CrossRefPubMedCentralPubMedGoogle Scholar
  87. Van Hemelrijck M, Ulmer H, Nagel G, Peter RS, Fritz J, Myte R, van Guelpen B, Foger B, Concin H, Haggstrom C, Stattin P, Stocks T (2018) Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria. PLoS One 13(6):e0197830CrossRefPubMedCentralPubMedGoogle Scholar
  88. Vaz M, Jennings G, Turner A, Cox H, Lambert G, Esler M (1997) Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 96(10):3423–3429CrossRefPubMedGoogle Scholar
  89. Wang YC, Colditz GA, Kuntz KM (2007) Forecasting the obesity epidemic in the aging U.S. population. Obesity (Silver Spring) 15(11):2855–2865CrossRefGoogle Scholar
  90. Warchol-Celinska E, Prejbisz A, Kadziela J, Florczak E, Januszewicz M, Michalowska I, Dobrowolski P, Kabat M, Sliwinski P, Klisiewicz A, Topor-Madry R, Narkiewicz K, Somers VK, Sobotka PA, Witkowski A, Januszewicz A (2018) Renal denervation in resistant hypertension and obstructive sleep apnea: randomized proof-of-concept phase II trial. Hypertension 72(2):381–390CrossRefPubMedGoogle Scholar
  91. Welle S (1995) Sympathetic nervous system response to intake. Am J Clin Nutr 62(5 Suppl):1118S–1122SCrossRefPubMedGoogle Scholar
  92. Westhoff JH, Hilgers KF, Steinbach MP, Hartner A, Klanke B, Amann K, Melk A (2008) Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension 52(1):123–129CrossRefPubMedGoogle Scholar
  93. Writing Group, M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB, C. American Heart Association Statistics and S. Stroke Statistics (2016) Heart disease and stroke statistics-2016 Update: a report from the American Heart Association. Circulation 133(4):e38–e360Google Scholar
  94. Xue B, Thunhorst RL, Yu Y, Guo F, Beltz TG, Felder RB, Johnson AK (2016) Central renin-angiotensin system activation and inflammation induced by high-fat diet sensitize angiotensin II-elicited hypertension. Hypertension 67(1):163–170CrossRefPubMedGoogle Scholar
  95. Yoon HE, Kim EN, Kim MY, Lim JH, Jang IA, Ban TH, Shin SJ, Park CW, Chang YS, Choi BS (2016) Age-associated changes in the vascular renin-angiotensin system in mice. Oxidative Med Cell Longev 2016:6731093CrossRefGoogle Scholar
  96. Young JB, Landsberg L (1997) Suppression of sympathetic nervous system during fasting. Obes Res 5(6):646–649CrossRefPubMedGoogle Scholar
  97. Zucker IH, Patel KP, Schultz HD (2012) Neurohumoral stimulation. Heart Fail Clin 8(1):87–99CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© American Aging Association 2018

Authors and Affiliations

  1. 1.Reynolds Oklahoma Center on AgingUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Physiological Sciences, Center for Veterinary Health SciencesOklahoma State UniversityStillwaterUSA

Personalised recommendations