Sex differences in the aging pattern of renin-angiotensin system serum peptidases.
Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants.



One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL).



Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (<55 years) men had significantly higher values of NEP serum activity than younger women. Significantly lower ACE serum activity was detected in older men compared to younger men. In women, significantly higher ACE2 serum activity was observed in older women compared to younger women.



These results suggest a differential effect of aging on the activity of RAS enzymes in men and women, especially with respect to the breakpoint of andropausia/menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.
Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Fernández-Atucha
Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
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Izagirre
Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Fraile-Bermúdez
Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Kortajarena
Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Larrinaga
Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
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Martinez-Lage
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Physiology, Faculty of Medicine, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Echevarría
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.|Department of Physiology, Faculty of Medicine, University of the Basque Country (UPV/EHU), P.O. Box 699, E-48080 Bilbao, Bizkaia Spain.
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Gil
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood*; D047649:Andropause / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008593:Menopause / Q000097:blood; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood*; D012084:Renin-Angiotensin System / Q000502:physiology; D012727:Sex Characteristics
D010447:Peptide Hydrolases
Aging; Renin–angiotensin system; Serum peptidases; Sex differences