Aging and the Renin-Angiotensin System

Conti, Sara; Cassis, Paola; Benigni, Ariela

doi:10.1161/hypertensionaha.110.155895

Cited by 94 publications

(96 citation statements)

References 62 publications

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“…This reduction is more pronounced in the upright posture and sodiumvolume depletion settings, where its serum levels are relatively lower than expected [1][2][3]. In rat aging models, this reduced plasma renin activity was documented to be associated with a reduction in renin synthesis in their juxtaglomerular apparatuses, which seem to be damaged during senescence [4].…”

mentioning

confidence: 88%

“…In rat aging models, this reduced plasma renin activity was documented to be associated with a reduction in renin synthesis in their juxtaglomerular apparatuses, which seem to be damaged during senescence [4]. All these chances consequently lead to a reduction in the function of the renin-angiotensin system (RAS) in the elderly [1][2][3][4]. However, despite the renin-angiotensin-aldosterone system (RAAS) activity decrease documented in the elderly, angiotensin II local secretion at the renal parenchyma is markedly increased.…”

mentioning

confidence: 99%

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Renin-angiotensin-aldosterone system and the aging kidney

Musso

Jáuregui

2014

Expert Review of Endocrinology & Metabolism

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confidence: 88%

mentioning

confidence: 99%

Renin-angiotensin-aldosterone system and the aging kidney

Musso

Jáuregui

2014

Expert Review of Endocrinology & Metabolism

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“…Angiotensin II signaling is a hallmark of activation of the renin-angiotensin system. CHF raises systemic levels of angiotensin II, whereas aging promotes local activation of the renin-angiotensin system without necessarily elevating circulating angiotensin II levels [125]. Importantly, angiotensin II infusion in mice causes diaphragm atrophy [126].…”

Section: Inflammatory and Neuroendocrine Factorsmentioning

confidence: 99%

Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology

Kelley

Ferreira

2016

Heart Fail Rev

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Inspiratory function is essential for alveolar ventilation and expulsive behaviors that promote airway clearance (e.g., coughing and sneezing). Current evidence demonstrates that inspiratory dysfunction occurs during healthy aging and is accentuated by chronic heart failure (CHF). This inspiratory dysfunction contributes to key aspects of CHF and aging cardiovascular and pulmonary pathophysiology including: i) impaired airway clearance and predisposition to pneumonia; ii) inability to sustain ventilation during physical activity; iii) shallow breathing pattern that limits alveolar ventilation and gas exchange; and iv) sympathetic activation that causes cardiac arrhythmias and tissue vasoconstriction. The diaphragm is the primary inspiratory muscle, hence, its neuromuscular integrity is a main determinant of the adequacy of inspiratory function. Mechanistic work within animal and cellular models has revealed specific factors that may be responsible for diaphragm neuromuscular abnormalities in CHF and aging. These include phrenic nerve and neuromuscular junction alterations as well as intrinsic myocyte abnormalities, such as changes in the quantity and quality of contractile proteins, accelerated fiber atrophy, and shifts in fiber type distribution. CHF, aging, or CHF in the presence of aging disturbs the dynamics of circulating factors (e.g., cytokines and angiotensin II) and cell signaling involving sphingolipids, reactive oxygen species, and proteolytic pathways, thus leading to the previously listed abnormalities. Exercise-based rehabilitation combined with pharmacological therapies targeting the pathways reviewed herein hold promise to treat diaphragm abnormalities and inspiratory muscle dysfunction in CHF and aging.

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“…Several groups demonstrated a tight link between RAS, mitochondria, and a host of age-related pathologic conditions (Inagami, 2011; Carey, 2012; Conti et al, 2012; Cook and Re, 2012; Dai et al, 2012; Ellis et al, 2012; Gao et al, 2012; Garcia et al, 2012; Gwathmey et al, 2012; Horan et al, 2012; Li et al, 2012; Singh et al, 2012; Wangler et al, 2012; Yu et al, 2012; Zaobornyj and Ghafourifar, 2012). In addition, RAS dysregulation aggravates several acute and chronic diseases, many of which have been linked to mitochondrial dysfunction [atherosclerosis (Warnholtz et al, 1999), kidney disease (Ma et al, 1998), myocardial damage after infarction (Kuno et al, 2002), cerebral infarct size after ischemia (Panahpour and Dehghani, 2012)].…”

Section: Mitochondria and Angiotensin System: Overviewmentioning

confidence: 99%

The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance

et al. 2014

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Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox) homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS). A main rate-controlling step in RAS is renin, an enzyme that hydrolyzes angiotensinogen to generate angiotensin I. Angiotensin I is further converted to Angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II binds with equal affinity to two main angiotensin receptors—type 1 (AT1R) and type 2 (AT2R). The binding of Ang II to AT1R activates NADPH oxidase, which leads to increased generation of cytoplasmic reactive oxygen species (ROS). This Ang II-AT1R–NADPH-ROS signal triggers the opening of mitochondrial KATP channels and mitochondrial ROS production in a positive feedback loop. Furthermore, RAS has been implicated in the decrease of many of ROS scavenging enzymes, thereby leading to detrimental levels of free radicals in the cell. AT2R is less understood, but evidence supports an anti-oxidative and mitochondria-protective function for AT2R. The overlap between age related changes in RAS and mitochondria, and the consequences of this overlap on age-related diseases are quite complex. RAS dysregulation has been implicated in many pathological conditions due to its contribution to mitochondrial dysfunction. Decreased age-related, renal and cardiac mitochondrial dysfunction was seen in patients treated with angiotensin receptor blockers. The aim of this review is to: (a) report the most recent information elucidating the role of RAS in mitochondrial redox hemostasis and (b) discuss the effect of age-related activation of RAS on generation of free radicals.

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Aging and the Renin-Angiotensin System

Cited by 94 publications

References 62 publications

Renin-angiotensin-aldosterone system and the aging kidney

Renin-angiotensin-aldosterone system and the aging kidney

Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology

The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance

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