What is aging? One can try to visually or analyze the condition of the organism, the degree of its wear and tear, but still what specific mechanisms are violated and what leads the organism to death – this is the main question that gerontological scientists ask. And here is what is known to date. The journal Cell in 2018 released an article on the main signs of aging, to which experts attributed genome instability, telomere shortening, epigenetic changes, disruption of new protein synthesis and nutrient recognition, mitochondrial damage, cellular aging, depletion of the stem cell pool and deterioration of intercellular interaction. Source: medach.pro Every year, new articles and books appear, in which scientists delve deeper and deeper into the mechanisms of the aging process. As a result, there are now a number of partly contradictory individual theories of aging based on observations about which processes are disrupted and where the first changes begin that eventually lead to damage and death of the entire organism. Dr. Kunlin Jin described the most comprehensive concept of aging theories and identified two main categories within it – theories of programmed aging and theories of damage and error. The former encompass age-related processes that occur within the body, the latter such as those that are manifested by environmental influences.

I. Theory of programmed longevity

A group of researchers led by Professor Gordon Lithgow from the Buck Institute of Aging in the 1990s offered an explanation about when longevity can occur during evolution. Leading scientists argue that aging is the result of sequentially turning certain genes on and off, and the timing of when such a program starts to kick in is determined by when age-related deficits manifest themselves. Supporters of this approach are convinced that information about destructive processes is in any case embedded in genes and no organism can avoid aging and death. However, with the help of mutations and short-term extreme influences, sometimes there is a failure in the program, which leads to an increase in the life span of individual species or individuals. Such results are helping to develop new ways to extend life.

II. Neuroendocrine theory

Proposed by the Russian endocrinologist and gerontologist Vladimir Dilman in 1968, this concept still does not lose its relevance, and on the contrary, with the development of technology strengthens its position. With the help of hormones synthesized in the body, the rate of activity of a living organism and all functional processes are controlled. With age, the number of cases of type 2 diabetes mellitus increases proportionally, menopause occurs in women and processes that negatively affect sexual function in men, the synthesis of hormones responsible for mood is disturbed, adrenal glands that secrete adrenaline function worse. Recent studies increasingly highlight the fact that aging is hormonally regulated and that the insulin signaling pathway, sex hormones and the system responsible for stress response play a major role in this.

III. Disruption of the regulation of the immune response

This is also one of the main explanations of the processes that change the organism and lead to aging. The first postulates of this theory were presented by an Australian scientist, Nobel Prize winner Sir Frank Macfarlane Burnet in the 50s. His ideas were later developed by Dr. Roy Lee Wolford and other researchers. The basic premise is that the immune system declines with age. This leads to increased vulnerability of the body, the development of infectious diseases and consequently aging and death. It is well known that immune efficiency peaks during puberty and gradually declines with age. As a person grows older, antibodies lose their effectiveness and the body fights new diseases worse, cellular stress occurs, which can lead to death. Dysregulation of the immune response has been shown to be associated with cardiovascular disease, inflammation, Alzheimer’s disease and oncology.

I. Theory of Wear and Tear

Cells and tissues have vital components that wear out with age from constant work, much like car parts. This leads to malfunction of the entire body and death. The theory of wear and tear was first proposed by Dr. August Weisman in 1882. It sounds perfectly reasonable even today because it is the kind of phenomena that happens to all material objects according to the laws of physics.

II. The theory of the speed of life

The postulate of this theory is that the higher the level of oxygen metabolism in an organism, the shorter its life span. The rate-of-life theory, while it may be useful, is not entirely adequate to explain maximum lifespan. In 2010, Canadian researcher David Rollo proposed a modified version of this concept that rigidly contrasts an organism’s growth and its resistance to stressful conditions.

III. Cross-linking theory

This theory of aging was proposed by biochemist Johan Bjorksten in 1942. According to it, the accumulation of cross-bridges – cross-links – chemically linking one protein to another, damages cells and tissues, slowing down processes in the body, which leads to aging. Modern research confirms that similar cross-links are formed between DNA molecules, irreversibly disrupting their normal functioning and leading to age-related changes.

IV. Free radical theory

This theory was first voiced in 1954 by Dr. Rebecca Gershman, but was developed in detail by biogerontologist Denham Harman in 1956. It suggests that superoxide and other free radicals cause damage to large molecules in the cells of the body, causing cells and eventually organs to stop functioning. The large molecules such as DNA, RNA, lipids, sugars and proteins that make up our cells have been proven to be affected by free radicals. The human body possesses some natural antioxidants (substances that inhibit oxidation) in the form of enzymes that help curb the dangerous accumulation of free radicals. Without these natural defenders, cell death rates would be much higher, resulting in a severely shortened lifespan for the body. Rodents that received antioxidants showed greater longevity.

In addition to this categorization, there are many other explanations for why all living things age and die and what processes are involved. After a century of aging research, the controversy over whether aging is an active or passive process continues unabated and a comprehensive theoretical model remains unclear. In 2018, Prof. Lucas Trindade and colleagues published a paper offering their breakdown of the theories into different categories. To answer the question of how aging processes occur in the body at the cellular and organismal level, theories of causation help in this categorization. These include telomere shortening, error accumulation, free radical damage due to oxidative stress, protein glycation, and others. Evolutionary theories, on the other hand, answer the question of why species aging occurs and how much of it is regular and genetically determined for populations as a whole. This division also takes into account all existing signs of aging and in many respects overlaps in content with the previous concept of Kunlin Jin, but provides a new perspective on the mutual intersection of causes leading to aging. Trindade’s classification of theories of aging. Source: www.ncbi.nlm.nih.gov In the end, what it all boils down to is that one can view aging as a process, look for changes within the body and ways to prevent such disruptions, and assess their impact on subsequent aging and death. Or one can focus on the causes of unlocking these mechanisms, whatever it may be due to – evolutionary and species specifics, environmental factors, or “counters” programmed within the organism.

Several theories have been proposed by science to explain the aging process, but there is currently no consensus on this issue. Many of the proposed theories of aging overlap with each other and it is not always possible to find a clear separation between them. However, with each study, with each new theory, mankind is one step closer to slowing down age-related processes and eventually defeating aging. Photo: www.haaretz.com