Mitochondrial quality control mechanisms as molecular targets in cardiac ageing

Anna Picca, Robert T. Mankowski, Jonathon L. Burman, Luca Donisi, Jae Sung Kim, Emanuele Marzetti, Christiaan Leeuwenburgh

Research output: Contribution to journalReview articlepeer-review

210 Scopus citations


Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Advancing age is a major risk factor for developing cardiovascular disease because of the lifelong exposure to cardiovascular risk factors and specific alterations affecting the heart and the vasculature during ageing. Indeed, the ageing heart is characterized by structural and functional changes that are caused by alterations in fundamental cardiomyocyte functions. In particular, the myocardium is heavily dependent on mitochondrial oxidative metabolism and is especially susceptible to mitochondrial dysfunction. Indeed, primary alterations in mitochondrial function, which are subsequently amplified by defective quality control mechanisms, are considered to be major contributing factors to cardiac senescence. In this Review, we discuss the mechanisms linking defective mitochondrial quality control mechanisms (that is, proteostasis, biogenesis, dynamics, and autophagy) to organelle dysfunction in the context of cardiac ageing. We also illustrate relevant molecular pathways that might be exploited for the prevention and treatment of age-related heart dysfunction.

Original languageEnglish
Pages (from-to)543-554
Number of pages12
JournalNature Reviews Cardiology
Issue number9
StatePublished - Sep 1 2018


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