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Renin-angiotensin System Blockade to Retard Aging
Posted on: September 29, 2010

Protein and lipid oxidation - mainly by mitochondrial reactive oxygen species (mtROS) – was proposed as a crucial determinant of life- and health span. Angiotensin-II enhances ROS production by activating NAD(P)H-oxidase and uncoupling endothelial-NOS. Angiotensin-II also stimulates mtROS production, which depresses mitochondrial energy metabolism.

In rodents, renin-angiotensin system blockade (RAS-bl) increases survival, and prevents age-associated changes. RAS-bl reduces mtROS, and enhances mitochondrial content and function. This suggests that angiotensin-II contributes to the aging process by prompting mitochondrial dysfunction.

Since angiotensin-II is a pleiotropic peptide, the age-protecting effects of RAS-bl are expected to involve a variety of other mechanisms. Caloric restriction – an age-retarding intervention in humans and animals – and RAS-bl, display a number of converging effects, i.e., they delay the manifestations of hypertension, diabetes, nephropathy, cardiovascular disease and cancer; increase body temperature; reduce body weight, plasma glucose, insulin and insulin-like growth factor-I; ameliorate insulin sensitivity; lower protein, lipid, and DNA oxidation, and mitochondrial H2O2 production, and increase UCP-2 and sirtuin expression. A number of these overlapping effects involve changes in mitochondrial function. In caloric restriction, PPARs seem to contribute to age-retardation partly by regulating mitochondrial function. RAS inhibition upregulates PPARs, therefore it is feasible that PPAR-modulation is pivotal for mitochondrial protection by RAS-bl during rodent aging. Other potential mechanisms that may underlie RAS-bl's mitochondrial benefits are TGF-beta downregulation and upregulation of Klotho and sirtuins.

Concluding, the available data suggests that RAS-bl deserves further research efforts to establish its role as a potential tool to mitigate the growing problem of age-associated chronic disease.

Source: de Cavanagh EM, Inserra F, Ferder L.; Angiotensin II blockade: a strategy to slow aging by protecting mitochondria?; Cardiovasc Res. 2010 Sep 6.
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