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Amelioration of the autonomic imbalances of old age with exercise: exploring the molecular and physiological mechanisms


There is considerable anecdotal evidence that a sedentary Iifestyle can lead to ill heath in old age, whereas physical activity has long-term health and wellbeing benefits. The reasons why homeostatic systems deteriorate in the elderly, and why exercise can ameliorate this deterioration, are not well understood. However, there is growing evidence that autonomic nervous system (ANS) imbalance is involved in a wide range of chronic conditions of old-age, such as hypertension. We hypothesize that the development and/or maintenance of the ANS imbalance is associated with changes in the expression of genes in the brain that, through their activity, form one or more functional networks can be influenced by both age and lifestyle factors, such as physical activity. In order to test this hypothesis, we will: i) identify putative gene networks by carrying out detailed and comprehensive transcriptome analysis on brain regions involved in the regulation of ANS of WKY rats compared to SHRs with a genetic predisposition to ANS imbalance characterized by over sympathetic activity related to gene expression changes as animals' age; iii) ask if gene expression is altered by physical exercise, initiated either before or after the onset of ANS imbalance; Iv) use bioinformatic tools to construct putative pathways and gene networks that may govern these processes to identify hub genes with many connections. Proof of principle studies will determine whether some of the age-related pathophysiology can be ameliorated. If so, these genes will undergo robust molecular, cellular and, physiological analysis that will reveal the roles of these hub genes in network stability and their response to external cues such as exercise. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Scientists attempt to identify key genes to control vital functions 

Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DAMPNEY, ROGER A.; MICHELINI, LISETE C.; LI, DE-PEI; PAN, HUI-LIN. Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular nucleus in normotensive and hypertensive states. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 315, n. 5, p. H1200-H1214, NOV 2018. Web of Science Citations: 8.
SANTOS, C. R.; RUGGERI, A.; CERONI, A.; MICHELINI, L. C. Exercise training abrogates age-dependent loss of hypothalamic oxytocinergic circuitry and maintains high parasympathetic activity. Journal of Neuroendocrinology, v. 30, n. 8, SI AUG 2018. Web of Science Citations: 2.
BUTTLER, LEILA; JORDAO, MARIA T.; FRAGAS, MATHEUS G.; RUGGERI, ADRIANA; CERONI, ALEXANDRE; MICHELINI, LISETE C. Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control. FRONTIERS IN PHYSIOLOGY, v. 8, DEC 12 2017. Web of Science Citations: 11.
SILVA, JR., SEBASTIAO D.; JARA, ZAIRA P.; PERES, ROSELI; LIMA, LARISSA S.; SCAVONE, CRISTOFORO; MONTEZANO, AUGUSTO C.; TOUYZ, RHIAN M.; CASARINI, DULCE E.; MICHELINI, LISETE C. Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction. PLoS One, v. 12, n. 12 DEC 12 2017. Web of Science Citations: 9.
ICHIGE, MARCELO H. A.; SANTOS, CARLA R.; JORDAO, CAMILA P.; CERONI, ALEXANDRE; NEGRAO, CARLOS E.; MICHELINI, LISETE C. Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure. JOURNAL OF PHYSIOLOGY-LONDON, v. 594, n. 21, p. 6241-6254, NOV 2016. Web of Science Citations: 10.
DE MOLO, VITOR U.; SALDANHA, RAYSSA R. M.; DOS SANTOS, CARLA R.; CRUZ, JOSIANE DE CAMPOS; LIRA, VITOR A.; SANTANA-FILHO, VALTER J.; MICHELINI, LISETE C. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats. FRONTIERS IN PHYSIOLOGY, v. 7, OCT 13 2016. Web of Science Citations: 5.
RAQUEL, HIVINY DE A.; MASSON, GUSTAVO S.; BARNA, BARBARA FALQUETTO; ZANLUQUI, NAGELA G.; PINGE-FILHO, PHILENO; MICHELINI, LISETE C.; MARTINS-PINGE, MARLI C. Swimming Training Modulates Nitric Oxide-Glutamate Interaction in the Rostral Ventrolateral Medulla in Normotensive Conscious Rats. FRONTIERS IN PHYSIOLOGY, v. 7, JUN 13 2016. Web of Science Citations: 0.
CHAAR, LAIALI JURDI; ALVES, TATIANA PEREIRA; BATISTA JUNIOR, ALVARO MARTINS; MICHELINI, LISETE COMPAGNO. Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas-The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats. PLoS One, v. 10, n. 9 SEP 15 2015. Web of Science Citations: 16.
MICHELINI, LISETE C.; O'LEARY, DONAL S.; RAVEN, PETER B.; NOBREGA, ANTONIO C. L. Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 3, p. H381-H392, AUG 1 2015. Web of Science Citations: 33.

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