Genome-Protecting Compounds as Potential Geroprotectors

Abstract

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

Prospective Associations of Tea Consumption With Risk of Cognitive Decline in the Elderly: A 1-Year Follow-Up Study in China

“…Moreover, polyphenols are the major active compounds present in teas, which have been proved to have beneficial effects against several pathological diseases including diabetes, cancer, and cardiovascular diseases ( 39 ). Most current research on the benefits of tea polyphenols mainly focuses on the following aspects, such as its antioxidation ( 40 ), hormesis ( 41 ), anti-inflammatory effects ( 42 ), re-allocation of energy ( 43 ), as well as DNA repair and conservation ( 44 ). We speculate that it is the interaction of these mechanisms that leads to the cognitive protective effect of consumption.…”

Effect of selective drugs that modulate the response to DNA damage on the radioresistance of Drosophila melanogaster

“…Ретиноевая кислота оказывает эффект на разные эпигенетические механизмы, тем самым влияя на различные механизмы репарации ДНК [6,13,22]. Описано, что она также повышает чувствительность клеток рака шейки матки человека к γ-облучению в результате экспрессии иммунологически важных поверхностных антигенов [23], т.е.…”

“…Ионизирующие излучения проявляют выраженную генотоксическую активность, поэтому в работе мы сконцентрировали внимание на веществах, способных модулировать ответ на повреждение ДНК и репарацию ДНК [6]. Выбранные нами соединения (ретиноевая кислота, эноксацин, KN-93 и UNC-0646) удовлетворяли следующим критериям: 1) являются селективными препаратами, нацеленными на конкретные мишени в клетке; 2) связаны с ответом на повреждение ДНК; 3) не идентифицированы как вещества, вызывающие повреждение ДНК.…”

Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

“…Several phytochemicals from fruits, vegetables, spices, teas, and medicinal plants may regulate epigenome and exhibit low toxicity in chronic administration (57). The applicability of major phytochemical groups such as polyphenols, terpenoids, organosulfur and alkaloids as epidrugs is experimentally established (58,59). In this section, the common protein targets for T2DM treatment and phytochemicals that modulate the activities of these proteins with antidiabetic activities in in silico, in vitro and in vivo studies are presented, while data related to clinical trials is shown in Table 1.…”