Introduction
In most countries, life expectancy has increased steadily in recent decades. In fact, the average life expectancy in 2015 rose worldwide to 71 years, compared to 46 years in 1950 [1]. Nevertheless, aging is an inevitable event that affects most of the living organisms over time. For most people, aging means getting old, having wrinkled skin and gray hair or even getting grandchildren. However, doctors and biologists consider aging to be a complex, multifactorial biological process in which there is a physiological loss of function that increases the susceptibility to environmental pollution and age-related chronic diseases such as cancer, metabolic disorders (e.g. type II diabetes), cardiovascular diseases and neurodegenerative diseases [2,3,4,5].
In order to identify potential therapeutic goals with which the aging process and the diseases mentioned above can be alleviated, numerous studies have been carried out to identify the changes caused by this process. As a result, nine characteristics of aging were defined, including genomic instability, changed intercellular communication, stem cell creation, cellular senescence as well as epigenetic changes and deregulation [6]. Together with other factors, these characteristics paved the way to identify molecular events that lead to an aging phenotype.
How do epigenetic changes affect the aging process?
1. DNA methylation
In view of the importance of epigenetics and great interest in the development of therapies that aim at epigenetic processes, great progress was made in this area in connection with aging. In fact, the DNA methylation - a biological process in which methyl groups are attached to the DNA molecule - was used as an indicator of the chronological age of cells and tissues such as blood, liver and kidney and therefore referred to as "epigenetic watch" [7]. In addition, changes in epigenetic patterns or the so-called "epigenetic drift" are a well-known phenomenon that describes the gradual decrease in global DNA methylation with the aging process [8].
It is important to consider that the DNA methylation patterns are not determined, but are reprogrammed in different stages of mammalian development. These patterns can change to various external and internal factors in response. However, it has been proven that global DNA hypomethylation (loss of methylation) is associated with aging [9,10]. This decrease in methylation is attributed to the progressive decline in the DNA methyltransferase DNMT1 [11]. Several genes have changed DNA methylation patterns in old age, e.g. B. genes for tumor suppression (LOX), development and growth (IGF2) and metabolism (ELOVL2), which provides information about the increased susceptibility to diseases [12].
2. Histon modification
Similarly, the aging has been proven to have an impact on the histone components of the chromatin. Histone can have a variety of post -translational modifications, which leads to enormous functional complexity that is still not fully understood. These modifications have been proven to have a variety of processes, e.g. B. on the gentranship, the DNA repair, the DNA replication and the condensation of chromatin [13,14]. The most important observed changes are the methylation and acetylation of lysin residues of the histones [15,16]. The tendencies of the age-related changes in histone methylation were examined in detail. So indicates z. B. the loss of certain trimethylation markings on H3 lysines (e.g. H3K9ME3 and H3K237ME3) to a general loss of the heterochromatic structure with aging [17,18]. In addition, technological advances have shown the opportunity to extend the life span in humans through sirtuin, a family of deacetylases with remarkable capabilities to prevent illnesses and to reverse aspects of aging in mice [19].
Changes in the heterochromatin - condensed DNA, which is usually not accessible to transcription - were observed in several organisms and are considered a classic model to explain aging [20]. The gradual loss of heterochromatic regions is mainly due to the loss of core protein of the chromatin. This transition from strongly condensed to weakly packed chromatin structures can lead to cellular dysfunctions. As a result, various consequences were observed, including a changed chromatin architecture, the decompression of dismissed genes and global changes in gene expression [21].
conclusion
Aging is a good example of a process in which research into epigenetics has made great progress and made an explanation for many dilemmata. The majority of the changes caused by aging is not yet fully understood. Together with partners, Moleqlar Analytics wants to develop epigenetic biomarkers that will help us to better understand why and how we age.
