Background-aim Aging is characterized by progressive adaptation influenced by both genetic and physiological factors. There are three possible kinds of aging: normal aging, aging associated with diseases that establishment when medical conditions occur and the successful aging that contemplate three principal components: a low probabil- ity of disease, a high cognitive and physical functional capacity, and an active engagement with life. During aging cardiovascular system undergoes substantial functional and structural changes altering the levels of some cardiac function biomarkers as natriuretic peptides (PN) and endothelin-1 (ET-1) and, recently, also the adrenomedullin (ADM) system has been identified as a new biomarker associated with aging but its role in this process is not yet defined. Aim was to evaluate the transcriptomic profile of the PN, ET-1 and ADM system in cardiac tissue of rats of different ages. Methods Three groups of male Wistar rats were studied: A (n = 6; age = 248 + 0.00 days-young), B (n = 13; age = 413.8 + 8.20 days-adult), C (n = 10; age = 597.6 + 10.3 days-old). Total RNA was extracted from cardiac tissue samples and analyzed by Real-Time PCR. Echocardiographic and histological evaluation completed the study. Results ANP and BNP mRNA levels resulted significantly higher in C (p b .01) with respect to A and B while CNP remained in a steady-state in B and C. NP receptors did not show any significant differences. ET-1 mRNA levels increased gradually and significantly as a function of age (A = 0.46 + 0.15; B = 1.50 + 0.33; C = 2.01 + 0.98; p = .013 A vs. B; p = .018 A vs. C). ET-A expression levels were statistically lower in B than A (p = .04) while ET-B were similar in all the three groups studied. The ADM showed a trend opposite to that of the other peptides studied, decreasing significantly as a function of age (A = 1.46 + 0.36; B = 0.64 + 0.17; C = 0.61 + 0.10; p = .04 A vs. B; p = .05 A vs. C) and presenting a counter-regulation of its main receptor complex CLRL and RAMP-2. Several significant correlations were observed between the analyzed genes and applying a multivariate logistic regression analysis, only LnANP (p = .003) and LnADM (p = .023) resulted significantly associated with aging. ADM trend suggests that the animals underwent to a successful aging as also confirmed by histological analysis that highlights a slight hypertrophy of cardiomyocytes and an increase in the expression of collagen fibers, a direct and non-pathological consequence of aging. Conclusions The study underlines the importance of a multi-label biomolec- ular approach in the evaluation of aging identifying, for the first time, ADM and ANP as independent aging markers and indicating the ADM as a possible predictor of successful aging.
Multi-label biomolecular approach to evaluate aging process: Transcriptomic profile study of cardiovascular biomarkers in cardiac tissue of rats as function of age
M Cabiati;S Del Ry
2019
Abstract
Background-aim Aging is characterized by progressive adaptation influenced by both genetic and physiological factors. There are three possible kinds of aging: normal aging, aging associated with diseases that establishment when medical conditions occur and the successful aging that contemplate three principal components: a low probabil- ity of disease, a high cognitive and physical functional capacity, and an active engagement with life. During aging cardiovascular system undergoes substantial functional and structural changes altering the levels of some cardiac function biomarkers as natriuretic peptides (PN) and endothelin-1 (ET-1) and, recently, also the adrenomedullin (ADM) system has been identified as a new biomarker associated with aging but its role in this process is not yet defined. Aim was to evaluate the transcriptomic profile of the PN, ET-1 and ADM system in cardiac tissue of rats of different ages. Methods Three groups of male Wistar rats were studied: A (n = 6; age = 248 + 0.00 days-young), B (n = 13; age = 413.8 + 8.20 days-adult), C (n = 10; age = 597.6 + 10.3 days-old). Total RNA was extracted from cardiac tissue samples and analyzed by Real-Time PCR. Echocardiographic and histological evaluation completed the study. Results ANP and BNP mRNA levels resulted significantly higher in C (p b .01) with respect to A and B while CNP remained in a steady-state in B and C. NP receptors did not show any significant differences. ET-1 mRNA levels increased gradually and significantly as a function of age (A = 0.46 + 0.15; B = 1.50 + 0.33; C = 2.01 + 0.98; p = .013 A vs. B; p = .018 A vs. C). ET-A expression levels were statistically lower in B than A (p = .04) while ET-B were similar in all the three groups studied. The ADM showed a trend opposite to that of the other peptides studied, decreasing significantly as a function of age (A = 1.46 + 0.36; B = 0.64 + 0.17; C = 0.61 + 0.10; p = .04 A vs. B; p = .05 A vs. C) and presenting a counter-regulation of its main receptor complex CLRL and RAMP-2. Several significant correlations were observed between the analyzed genes and applying a multivariate logistic regression analysis, only LnANP (p = .003) and LnADM (p = .023) resulted significantly associated with aging. ADM trend suggests that the animals underwent to a successful aging as also confirmed by histological analysis that highlights a slight hypertrophy of cardiomyocytes and an increase in the expression of collagen fibers, a direct and non-pathological consequence of aging. Conclusions The study underlines the importance of a multi-label biomolec- ular approach in the evaluation of aging identifying, for the first time, ADM and ANP as independent aging markers and indicating the ADM as a possible predictor of successful aging.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
