Down-regulation of the intrarenal renin-angiotensin system in the aging rat.

Abstract

Progressive deterioration of renal function occurs during normal aging. Previous studies on the aging kidney have demonstrated glomerular hemodynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibition have relatively less proteinuria and sclerosis, suggesting that age-related changes in renal function may be associated with alterations in the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examined at an early phase of the aging process (3 months) and at a later phase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ significantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angiotensinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in older rats. Thus, both decreased renin synthesis and impaired renin release underlie the fall in plasma renin with normal aging. This decrease may act to lower intrarenal baseline levels of angiotensin II, an adaptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney.

Global and tissue-specific aging effects on murine proteomes

“…These age-related differences reflect tissue-specific features related to aging decline. For example in kidney, there was reduced abundance of BCAT1, which promotes mitochondrial biogenesis and ATP production and has been shown to promote breast cancer formation when knocked down 17 , and REN1, which has been shown to play a role in modulating vascular tone and tubular function in the kidney 18 . For sex effects, we detected 1,006 proteins with consistent differences between sexes across tissues and 2,565 proteins with tissue-specificity.…”

Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?

“…A specific condition of generally increased signal intensity and/or complexity is stress, which desensitises a wide range of signals [ 74 – 81 ]. Ageing can be perceived as a result of cumulative stress [ 82 – 86 ], which downregulates a large number of signalling pathways [ 87 – 91 ].…”

“…Ageing can be perceived as a cumulative result of the continuous stress by free radicals and other harmful effects inducing inflammation [ 82 – 86 ]. Ageing is downregulating the renin-angiotensin system in rat kidneys [ 87 ]. Klotho-induced activation of the retinoic acid-inducible gene I/nuclear factor-κB (RIG-I/NF-κB) signalling pathway, as well as the subsequent production of proinflammatory mediators (TNF α and interleukin-6) and inducible nitric oxide synthase were reduced in the kidneys of aged senescence-accelerated mouse prone-8 (SAMP8) mice [ 88 ].…”

Premature Aging in Chronic Kidney Disease: The Outcome of Persistent Inflammation beyond the Bounds

“…The juxtamedullary apparatus of the kidney secretes renin. In elderly individuals, plasma renin and aldosterone levels are reduced by 40-60% and 30-50%, respectively [57,58], thereby decreasing potassium excretion capacity and increasing the risk of hyperkalemia and sensitivity toward drugs that inhibit urinary potassium excretion, such as potassium-sparing diuretics [59].…”