Publication

Derailed Proteostasis as a Determinant of Cardiac Aging

Wiersma, M., Henning, R. H. & Brundel, B. J. J. M., Sep-2016, In : Canadian Journal of Cardiology. 32, 9, p. 1166.e11-20 10 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Age comprises the single most important risk factor for cardiac disease development. The incidence and prevalence of cardiac diseases, which represents the main cause of death worldwide, will increase even more because of the aging population. A hallmark of aging is that it is accompanied by a gradual derailment of proteostasis (eg, the homeostasis of protein synthesis, folding, assembly, trafficking, function, and degradation). Loss of proteostasis is highly relevant to cardiomyocytes, because they are postmitotic cells and therefore not constantly replenished by proliferation. The derailment of proteostasis during aging is thus an important factor that preconditions for the development of age-related cardiac diseases, such as atrial fibrillation. In turn, frailty of proteostasis in aging cardiomyocytes is exemplified by its accelerated derailment in multiple cardiac diseases. Here, we review 2 major components of the proteostasis network, the stress-responsive and protein degradation pathways, in healthy and aged cardiomyocytes. Furthermore, we discuss the relation between derailment of proteostasis and age-related cardiac diseases, including atrial fibrillation. Finally, we introduce novel therapeutic targets that might possibly attenuate cardiac aging and thus limit cardiac disease progression.

Original languageEnglish
Pages (from-to)1166.e11-20
Number of pages10
JournalCanadian Journal of Cardiology
Volume32
Issue number9
Publication statusPublished - Sep-2016

    Keywords

  • DESMIN-RELATED CARDIOMYOPATHY, UNFOLDED PROTEIN RESPONSE, HUMAN ATRIAL-FIBRILLATION, LIFE-SPAN EXTENSION, HEAT-SHOCK RESPONSE, OXIDATIVE-STRESS, CAENORHABDITIS-ELEGANS, CONTRACTILE DYSFUNCTION, DROSOPHILA-MELANOGASTER, CALORIC RESTRICTION

ID: 35192126