**Abstract**

The history of active worldwide scientific research on mechanisms of aging and the age-associated diseases counts more than five decades. Of these, among the numerous theories of aging, at least 50 years dominated the free radical theory of aging. Since mitochondria were found to be the major producers of free radicals, the research on aging became largely centered on mitochondria. At the end of 80s of the 20th century, physicians have established a new nosological entity named "Metabolic syndrome" comprising several simultaneously existing symptoms and risk factors, which increase with age to 47% in men and 64% for women. The diagnosis of metabolic syndrome (MetS) requires simultaneous presence of at least three out of five medical conditions: visceral obesity, hypertension, high blood sugar, insulin resistance, low serum high-density lipoprotein accompanied with high serum triglycerides. However, from the beginning of the definition of MetS there was, and still is, a rather lovely debate, which of the symptoms must be considered as the main one. In spite of the enormous number of publications on both mechanisms of aging and MetS, there was relatively small progress in understanding the fundamental processes in these closely related problems. On the contrary, the mitochondrial free radical theory was found to be wrong in its current paradigms. In this Chapter we will discuss recent discoveries and hypotheses which open new perspectives in both theoretical and practical approaches to the problems of aging and MetS. We will show how aging and development of MetS are closely related to each other and the normal ontogenesis of human beings. Why men and women have different rates of aging and mechanisms of transition to MetS. We state that MetS is not just a cluster of symptoms, but one of the last steps of individual ontogenesis, namely the first step of eldership when the aging rate may increase manifold.

**Keywords:** aging, eldership, energy metabolism, fatty acid oxidation, isoprostane lipid peroxidation, mitochondrial DNA, metabolic syndrome, obesity, ontogenesis, oxidative stress, perhydroxyl radical, reactive oxygen species, ROS, superoxide radical, type 2 diabetes

## **1. Introduction**

Everybody wants to live a long and healthy life. However, the universal laws of the Irreversible Thermodynamics drive changes in our bodies from the moment of birth,

when a human baby has maximum information in his genes and minimum entropy in his body, through a series of consecutive changes to the last stage, when a human body has much less information left in the remaining old genes and maximum entropy in his body, which finally fails and the person dies.

We intentionally started our Chapter by mentioning the genetically predetermined stages of development of the human organism because, as it happened, the concept of ontogeny was somehow lost during the decades of research on mechanisms of aging and metabolic syndrome. As we will see, this approach gives completely different perspectives on the problems from the point of view of normal postembryonic ontogenesis.

The problems of aging and life longevity are not just medical problems, but are complex of fundamental biological problems, which comprise evolution, ontogenesis, genetics, epigenetics, and interactions with the environment. For this reasons, researchers studied aging and longevity starting from simple organisms like yeast and worms, then more complex laboratory animals, and even species like crocodiles and birds. Humans are, probably, much less studied in this respect than, say, mice and rats. To this day there are dozens of aging theories, which reflect the complexity of the problem. We mention only few of the relatively recent theories of aging: The heterochromatin loss model [1, 2]; adult stem cell and mesenchymal progenitor theory [3]; hormonal regulation of longevity in mammals [4]; telomere hypothesis of aging [5, 6]; epigenetic theory [7], and finally, currently the most popular and experimentally developed the free radical hypothesis of aging [8–21]. All theories of aging and longevity are interrelated, but so far, there is no generalizing theory. Therefore, we will start our discussions on human aging mechanisms from the currently most important theory of aging: the mitochondrial free radical theory.
