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Publication : Biological sex, sex steroids and sex chromosomes contribute to mouse cardiac aging.

First Author  Morin-Grandmont A Year  2024
Journal  Aging (Albany NY) Volume  16
Issue  9 Pages  7553-7577
PubMed ID  38742935 Mgi Jnum  J:348837
Mgi Id  MGI:7644047 Doi  10.18632/aging.205822
Citation  Morin-Grandmont A, et al. (2024) Biological sex, sex steroids and sex chromosomes contribute to mouse cardiac aging. Aging (Albany NY) 16(9):7553-7577
abstractText  After menopause, the incidence of cardiovascular disease rapidly rises in women. The disappearing protection provided by sex steroids is a consequence of the development of many risk factors. Preclinical studies are necessary to understand better the effects of ovarian hormones loss cardiac aging. To mimic menopause in mice and study its consequences, we delayed ovariectomy at 12 months and followed animals for 12 months. Using RNA sequencing, we investigated changes in the myocardial exome with aging. In addition, with four-core genotypes (FCG) transgenic mice, we studied sex chromosome effects on cardiac aging. Heart weight increased from 3 to 24 months (males + 35%, females + 29%). In males, 75% of this increase had occurred at 12 months; in females, only 30%. Gonadectomy of mice at 12 months blocked cardiac hypertrophy in both sexes during the second year of life. The dosage of the X chromosomes did not influence cardiac growth in young and older mice. We performed an RNA sequencing study in young and old mice. We identified new highly expressed genes modulated during aging (Bdh, Myot, Cpxm2, and Slc38a1). The myocardial exome in older animals displayed few differences related to the animal's sex or the presence or absence of sex steroids for a year. We show that the morphological evolution of the heart depends on the biological sex via gonadal sex hormone actions. The myocardial exome of old male and female mice is relatively similar. Our study emphasizes the need to consider sex steroid effects in studying cardiac aging.
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