Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

Abstract

Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies.

Effects of estrogen on glutathione and catalase levels in human erythrocyte during menstrual cycle

“…Oxidative stress is responsible for aging and coronary heart diseases (10,11). Rapid induction of intracellular GSH synthesis occurs in response to various oxidative stress parameters, which is a critical determinant of cellular tolerance to oxidative stress (12).…”

Epigenetic Alterations in Aging and Aging-Associated Diseases: Review

“…[28,29] DNA metilasyonu gelişim ve farklılaşma, genomik imprinting, X kromozomunun inaktivasyonu, genomu transpozonlardan koruma gibi farklı biyolojik fonksiyonlara aracılık etmektedir. 19,28,30 DNA metilasyon düzeyinin yaşlanmaya bağlı olarak değişimi çeşitli çalışmalarda gösterilmiştir. Yaşlanma ve DNA metilasyonu arasındaki ilişki ilk kez somon balığında yapılan çalışmalarda öne sü-rülmüştür.…”

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“…It is still unclear whether this modification also interferes with 5mC reading. Moreover, the double-modified CpG islands have been assumed to promote amyloid deposit formation in the brain [61].…”

“…Concerning antioxidative protection, the capacity of melatonin of preventing 8-hydroxy-deoxyguanosine formation by hydroxyl radicals [59,60] has been discussed [11]. If 8-hydroxy-dG (which easily turns into its tautomer 8-oxo-dG) is formed in CpG islands containing 5mC, the double modification prevents DNA repair [61]. 8-oxo-dGmay already inhibit the binding of Tet enzymes or of thymine DNA glycosylase (TDG), the key enzyme of base excision repair.…”