**Molecular Signal Integration of Aging and Diabetes Mellitus Mellitus**

**Molecular Signal Integration of Aging and Diabetes** 

DOI: 10.5772/intechopen.70699

#### Irina Sarvilina Irina Sarvilina Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70699

#### **Abstract**

DM is considered as the cause of accelerated aging. Numerous biomedical studies have proved the key role of neuroimmune-endocrine interactions in the human body, which trigger the universal molecular pathways in the development of aging and DM (GH/IGF-1, Ras-MAPK, FOXO3A, sirtuin, mTOR, CETP, Timeless gene, TZAP pathways). Modern methods of proteomic and bioinformatic analysis allow us to investigate key genomicproteomic interactions that underlie diabetic nephropathy (DN) in patients with type 2 DM. The study of the formation and development of DN can become the model for studying molecular pathways of aging of kidney tissue. Future biomedical research based on methods of high-throughput screening (HTS) of a pool of target molecules will lead to great advances in the diagnosis of aging stages and DM, as well as the development of methods for the prevention and therapy of accelerated aging of the human body and various violations of carbohydrate metabolism (1D-2D/MALDI-TOF-MS, HTS, biochips, biosensors).

**Keywords:** aging, diabetes mellitus, pathway, gene expression, proteomics

#### **1. Introduction**

The latest data show that the prevalence of diabetes mellitus (DM) in the world has increased more than in two times, peaking at 415 million by the end of 2015 [1]. In accordance with the current evaluation of the International Diabetes Federation, 642 million patients will be with DM by 2040 [2]. Increased incidence of DM caused the adoption of the United Nations (UN) resolution 61/225 dated 20 December 2006 about DM. In the 2011, political declaration was adopted by the UN to the national healthcare systems to create a multidisciplinary strategy in the area of prevention and control of noninfectious diseases, where particular attention is drawn to the problem of DM as one of the leading causes of disability and mortality [3].

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

There is significant increase of the prevalence of DM in the Russian Federation. According to the Federal Register of Diabetes Mellitus, at the end of 2016, 4.35 million outpatients with DM (3% of the total population) were registered in Russia, of whom 92% (4 million people) had type 2 DM, 6% (255,000 people) - type 1 DM and 2% (75,000 people) -other types of DM. Actual number of patients with DM remains underestimated, since only identified and reported cases are considered. The results of the large-scale Russian epidemiological study NATION confirmed that only 50% of type 2 DM cases are diagnosed. Actual number of patients with DM can be at least 8-9 million people (about 6% of the population) in Russia [4]. Because of the lack of timely diagnostics of DM, some patients do not receive necessary therapy and have higher risk of the developing of such complications of DM as retinopathy, nephropathy, ischemic heart disease, cerebral ischemia, peripheral angiopathy. These complications are responsible for most cases of disability and mortality of DM.

to the presence of neuronal processes, receptors and neurotransmitters in the nervous system, as well as the presence of highly mobile cell elements and cytokines in the immune system [7]. The search of opportunities of the influence to immune processes through the central nervous system in the order to prevent of aging and metabolic disorders is based on fundamental laws of hierarchical organization of regulatory system, the presence of humoral signals in cell populations, the points of application of the effect in tissues and organs. The information in the nervous system is encoded in the sequence of electrical impulses and in the architecture of neuronal interactions, in the immune system information is stored in stereochemical configuration of molecules and receptors involved in lymphocyte interactions. There was evidence of a common receptor apparatus in the immune system to neuromediators and nervous system to endogenous immunomodulators. Immunological active neuroendocrine substances - thymosin, triiodothyronine (T3) and thyroxine (T4), protimosin, endogenous regulator of protimosin, parathymosin, oxytocin, Th-I antigen and vasoactive intestinal peptide have been found both in the brain and in the thymus, they play significant role in the aging of human immune system [8]. The greatest number of studies are devoted to the participation of interleukin 1 (IL-1), in immunoregulation at the level of immunocompetent cells and in regulation of functions. Interleukin 2 (IL-2) also exerts various effects on the immune and nervous systems mediated by affinity binding to the corresponding cell surface receptors. The activating effect of IL-2 on lymphocytes and macrophages is manifested in the enhancement of the antibody-dependent cytotoxicity of these cells with parallel stimulation of the secretion of tumor necrosis factor α (TNF-α). IL-2 induces proliferation and differentiation of oligodendrocytes, affects the reactivity of the hypothalamus neurons and increases the level of adrenocorticotropic hormone (ACTH) and cortisol in the blood, which together form a stable mechanism of neuroimmune and neuroendocrine network interactions. Cells that are targets for the action of IL-2 are T-lymphocytes, natural killers (NK), and macrophages. IL-2 causes the functional activation of these cell types and the secretion of other cytokines, for example, increases the production of NK cells by interferon γ (IFN-γ) [9]. There are data about the production of nervous cells of IL-1, IL-6 and TNF-α, which are critical components in the development of chronic inflammation with destruction of β-cells of the pancreas in DM type 2 [10]. It is known that glucocorticoids (GCs), androgens, estrogens and progesterone suppress immune responses, and growth hormone (GH), T4 and insulin have a stimulating effect [11, 12]. Cells of the immune system transmit transmembrane signal to receptors for GCs, insulin, GH, estradiol, testosterone, betaadrenergic agents, acetylcholine, endorphins and enkephalins [13]. All of above-mentioned hormonal factors are involved in the formation of metabolic and immunological changes in conditions of aging and DM. For example, the exogenous administration of contra-insular hormones T3 and T4 alters functional activity of the immune system. This action is realized through cytoplasmic and nuclear receptors in immune cells [14, 15]. The theory of aging suggests that life expectancy has negative relationship with metabolic rate, which is regulated by hormones of energy metabolism. Experimental hypothyroidism increased life expectancy in young rats, whereas hyperthyroidism shortened life expectancy. Several mutant mice in long life experiment had reduced or almost absent thyroid function [16–18]. Hypothyroidism can affect life expectancy by reducing the intensity of metabolism, body temperature and oxygen consumption, resulting in a decrease in the generation of free oxygen radicals and associated oxidative damage in cells. Subclinical hypothyroidism is associated with a reduction

Molecular Signal Integration of Aging and Diabetes Mellitus

http://dx.doi.org/10.5772/intechopen.70699

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Today, DM is considered as the cause of accelerated aging [5]. Twenty percent of middleaged people and 35% of the population of older persons are characterized by varying degrees of impaired glucose tolerance (IGT) and symptoms of insulin resistance. An increase in the frequency of obesity and sedentary lifestyle and the major risk factors for type 2 DM suggests that the prevalence of DM in the world will increase. The management of this disease becomes difficult for persons aged 60, 70 and 80 years. The risk of complications, such as ischemic heart disease, increases with age, as well as damage with age of organs of vision, hearing and physical activity, can amplify in the presence of DM.

The modern stage of the development of researches in the field of DM and aging is interrelated and involves the use of unified technological platforms for molecular diagnostics and pharmacology of stages of aging and DM. Unified technological platforms presuppose the performing of comparative genomic and proteomic studies, the results of which allow to study interrelated pathogenesis of aging and DM. Also new technological platforms are necessary for the development of new prophylaxis and treatment of these interconnected pathological states. The analysis of data from comparative genomic and proteomic studies allows the formation of unified molecular pathological pathways of DM and aging. The chapter presents new technological platforms for the early identification and the development of anti-aging and anti-diabetic agents.
