Exercise-mitigated sex-based differences in aging: From genetic alterations to heart performance

Denise Börzsei, Dániel Priksz, Renáta Szabó, Mariann Bombicz, Zoltán Karácsonyi, László G. Puskás, Liliána Z. Fehér, Zsolt Radák, Krisztina Kupai, Anikó Magyariné Berkó, Csaba Varga, Béla Juhász*, Anikó Pósa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The prevalence of cardiovascular diseases dramatically increases with age; therefore, striving to maintain a physiological heart function is particularly important. Our aim was to study the voluntary exercise-evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running groups. After the 12-wk-long experimental period, echocardiographic measurements were performed. Afterwards, hearts were either removed for biochemical measurements or mounted into a Langendorff-perfusion system to detect infarct size. The following genes and their proteins were analyzed from heart: catechol-O-methyltransferase (Comt), endothelin-1 (Esm1), Purkinje cell protein-4 (Pcp4), and osteoglycin (Ogn). Recreational exercise caused functional improvements; however, changes were more prominent in males. Cardiac expression of Comt and Ogn was reduced as a result of exercise in aged males, whereas Pcp4 and Esm1 showed a marked overexpression, along with a markedly improved diastolic function. The key result of this study is that exercise enhanced the expression of the Pcp4 gene and protein, a recently described regulator of calcium balance in cardiomyocytes, and suppressed Comt and Ogn gene expression, which has been associated with impaired cardiac function. In addition, as a result of exercise, a significant improvement was observed in the size of infarct elicited by left anterior descending coronary artery occlusion. Our results clearly show that age and sex-dependent changes were both apparent in key proteins linked to cardiovascular physiology. Exercise-moderated fundamental genetic alterations may have contributed to the functional adaptation of the heart. NEW & NOTEWORTHY Voluntary exercise has proved to be an effective therapeutic tool to improve cardiac function in aged rats with clearly visible sex differences. Long-term exercise is associated with decreased Ogn and Comt expression and enhanced presence of Pcp4 and Esm1 genes. Sex-dependent changes were also observed in the expression of the cardiovascular key proteins. Fundamental alterations in gene and protein expression may contribute to the improvement of cardiac performance.

Original languageEnglish
Pages (from-to)H854-H866
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
Publication statusPublished - 2021 Feb
Externally publishedYes


  • Aging
  • Echocardiography
  • Exercise
  • Gene expression
  • Pcp4

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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