Abstract
Cardiovascular diseases (CVDs) are the most serious health problem in the world, displaying high rates of morbidity and mortality. One of the main risk factors for CVDs is age. Indeed, several mechanisms are at play during aging, determining the functional decline of the cardiovascular system. Aging cells and tissues are characterized by diminished autophagy, causing the accumulation of damaged proteins and mitochondria, as well as by increased levels of oxidative stress, apoptosis, senescence and inflammation. These processes can induce a rapid deterioration of cellular quality-control systems. However, the molecular mechanisms of age-associated CVDs are only partially known, hampering the development of novel therapeutic strategies. Evidence has emerged indicating that noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and micro RNAs (miRNAs), are implicated in most patho-physiological mechanisms. Specifically, lncRNAs can bind miRNAs and act as competing endogenous-RNAs (ceRNAs), therefore modulating the levels of the mRNAs targeted by the sponged miRNA. These complex lncRNA/miRNA/mRNA networks, by regulating autophagy, apoptosis, necrosis, senescence and inflammation, play a crucial role in the development of age-dependent CVDs. In this review, the emerging knowledge on lncRNA/miRNA/mRNA networks will be summarized and the way in which they influence age-related CVDs development will be discussed.
Highlights
IntroductionBetter healthcare and living conditions have contributed to an increase in people’s longevity, which has resulted in a higher prevalence of age-related debilitating and life-threatening diseases such as cardiovascular diseases (CVDs), cancer and neurodegeneration
Better healthcare and living conditions have contributed to an increase in people’s longevity, which has resulted in a higher prevalence of age-related debilitating and life-threatening diseases such as cardiovascular diseases (CVDs), cancer and neurodegeneration.CVDs share with infectious diseases the worst rate of morbidity and mortality, with more than 30% of all deaths worldwide according to the World Health Organization [1], and it is expected that, as the world population ages, this situation will worsen [2,3].age represents a major independent risk factor for cardiovascular-related morbidity and mortality [4,5]
As described in the previous sections, the affinity of the micro RNAs (miRNAs) binding site, the ability of the miRNA to induce the degradation of the bound RNA, the relative abundance of direct players are some of the elements that contribute to the complexity of long ncRNAs (lncRNAs)/miRNA/mRNA networks, determining the biological outcome
Summary
Better healthcare and living conditions have contributed to an increase in people’s longevity, which has resulted in a higher prevalence of age-related debilitating and life-threatening diseases such as cardiovascular diseases (CVDs), cancer and neurodegeneration. CVDs share with infectious diseases the worst rate of morbidity and mortality, with more than 30% of all deaths worldwide according to the World Health Organization [1], and it is expected that, as the world population ages, this situation will worsen [2,3]. There are several pieces of evidence reporting that ncRNAs are causally linked to the development of age-associated CVDs by regulating inflammation, cell proliferation, apoptosis, senescence and autophagy. We will review and summarize the mechanistic, functional, and pathological role of the lncRNAs/miRNAs/mRNA networks in these events and their specific involvement in age-related CVDs
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