The need to find any ‘cure’ is based upon discovering the source of the origin of the disease. This remains as true to antiaging medicine as it does to mainstream medicine. However the origins of degenerative aging are more difficult to ascertain as the problems appear to be multi-factional. This article sets out to briefly describe some of the most ‘forthright and treatable’ theories of aging, highlighting the fact that in order to abide by the policy of measure-treat-measure, and to affect the core of the problem, that attention to both the biomarkers of aging, as well as the theories themselves are necessary.
I have been lucky enough to be involved in antiaging medicine for nearly 20-years. My pharmacy, food and vitamin technology and biochemistry experience has covered various aspects of international database research, working along with many professional people, and in helping to establish criteria for aging biomarkers based on published evidence. But this isn’t a job application! I am trying to impart that having attended numerous conferences and meetings, read much of the literature and communicated with leaders in the antiaging field and I believe that if we want to truly bring about an end to degenerative aging, or at least control it in a masterful way, then we must pay close attention to the theories of aging. By so doing we can truly target and test the effectiveness of different antiaging protocols. However, the theories of aging and their measurement is something that is rarely mentioned at antiaging meetings or in submissions. Should we not expect that any protocol or product to give reference to the type(s) of theories of aging that it may be addressing? In this article I hope to outline some of the “best” proposed theories.
Our first problem is to define aging itself. Once defined we can present a clear reasoning behind what we mean by antiaging medicine, i.e., what we intend to achieve as a positive outcome. A definition of aging was reported in ancient Greek philosophy. According to Aristotle the human body is composed of 4 elements: humid, dry, warm and cold. The humid and warm prevail while we are young, while the dry and cold take predominance as we get older. Modern biology has produced a more sophisticated definition of aging. Strehler (1) suggested that the aging process has 4 main characteristics:
- It is destructive, (i.e., it decreases function).
- It is progressive, (i.e., an ongoing process).
- It is intrinsically determined, (i.e., it is bound to internal characteristics and does not depend entirely on external factors).
- It is universal, (i.e., all species exhibit aging phenomena).
This definition of aging has never been contested; consequently awareness of this definition is a requirement for any serious aging theory.
The theories of aging
Some of the earliest theories of aging were called the somatic mutations (2-5), later versions became known as genetic mutations, or even error catastrophe theories (6-9). Much was originally made about exposure to “cosmic radiation.”
The wear and tear explanations of aging began with Erasmus Darwin (10) and they have been maintained in different forms until today. This approach does not blame external factors for aging, but the increasing incapacity of the organisms for effective self-repair.
The glycosylation or cross-linking theory of aging attributes the formation of intra and intermolecular cross-links that alter the structure of the macromolecules, so much so that their functions become compromised. This explanation was suggested by Björksten in 1942 (11) and King in 1946 (12) and confirmed by experimental demonstration by Verzár in the 1950’s (13-15). In fact, Fritz Verzar somewhat jokingly said: “The main question of basic aging research was to find out, why an old chicken requires a much longer time of cooking, than a young one!” (16)
Perhaps the best known theory of aging is the free radical. It was Denham Harman in 1956 (17, 18) who proposed that free radicals might be involved in the age-dependent deterioration of the molecular structure. There is however a paradox arising from the fact that young individuals consume more oxygen per unit mass/ time than the old ones. Consequently, there must be an even higher rate of free radical generation at younger ages. Yet young organisms are able to grow and proliferate, i.e., they remain apparently untouched by the free radicals, while the older organisms become progressively deteriorated by the very same free radicals, even at a much lower rates of formation. (19)
The accumulation theories of aging assume that aging is caused by the increasing prevalence of certain substances such as lipofuscin, (age pigment), aged collagen, damaged neurofibrils, damaged enzymes, etc. Indeed, lipofuscin has been considered as one of the most significant biomarker of aging (20). Chemically speaking, lipofuscin is a strongly altered, extensively cross-linked, mainly insoluble, lipoprotein mass. Its presence in cells appears to increase with age and it is found in abundance in the brains of Alzheimer Disease patients.
First exposed by Vladimir Dilman in 1987 this focuses on the loss of sensitivity of the receptors with aging, along with the loss of control over the endocrine system via the pituitary/ hypothalamus axis. The resulting hormonal disarray cascades into the varying degenerative aspects of aging. (21)
Whilst aligned with the free radical theory and originally also proposed by Denham Harman in 1972 (22), it was expanded upon by Jamie Miquel in 1980 (23). During mitochondrial production of the universal energy molecule adenosine triphosphate, (through the facilitation of the Krebs and electron transport chain cycles), the mitochondria produce some of the most damaging free radicals, specifically the superoxide radical, hydrogen peroxide and the hydroxyl radical (24). However, the very uniqueness of mitochondrial DNA, (mtDNA) is also a weakness as it has no histone protection or enzyme repair systems to offer itself significant free radical protection (25). Linnane et al examined skeletal muscle samples from a 5 year old and a 90 year old human. They found that whilst nearly all the mtDNA of the 5-year old were full-length, less than 5% were still full length in the 90-year old. (26) Mitochondrial oxidative damage and decreased function has been cited as a key factor in Parkinson’s disease (27). The mitochondrial theory hinges on this formula:
Less mitochondrial oxidant generation = less mtDNA damage and less mtDNA damage = more normal mitochondrial bioenergetics throughout life (28).
There is some evidence (at least in animals) that females have less mitochondrial damage than males, which may help to explain why as a species they live longer than males. (29)
The membrane hypothesis of aging was developed in the late seventies (30, 31) and published by Imre Zs.-Nagy in 1994 (20). Zs.-Nagy notes that the accumulation of dry mass is an implicit requirement during development and maturation of every living being. This accumulating dry mass and loss of intracellular water content of cells inhibits enzyme activity as well as heat and chemical transference and cell “communication.”
Although not yet published, Walter Pierpaoli has eloquently described it at many meetings and has promised that he will publish it soon, although much of that work can be read in well documented melatonin experiments (33, 34). In effect it is the wake; sleep cycle that triggers “a clock” contained within the pineal gland that effectively monitors the circadian rhythms, hence the propensity for very few human beings to live beyond 120 (a number you may remember also suggested in the Bible). His animal experiments highlighted that grafting an old pineal into a young mouse and grafting the young pineal into the old mouse accelerated the aging of the young mouse dramatically, but in turn reversed the aging of the old mouse. It would appear that the pineal clock can be “tricked” into resetting itself through the use of melatonin and perhaps other pineal and hypothalamic hormones (33, 34).
There are numerous other theories of aging including the theory of autoimmunization, the decomposed program, the organic explanations (32), and of course the varying genetic theories of aging such as shortening telomeres. Doubtless in the years to come more will be promoted.
It is clear that many theories of aging are inter-related, perhaps a case of which comes first the chicken or the egg? However, the frustration present today in antiaging medicine is that the majority of therapies are based on the replacement of “missing” substances in older age, (i.e., hormones, minerals, vitamins, etc.). Many of these replacement therapies are well documented to improve lost functions, enhance immunity etc., they may likely lead onto preventative roles, but until we have a really solid and generally accepted aging theory, no real chance of a precise antiaging intervention may be designed and adopted.
If it were, such an approach would certainly silence the critics of antiaging medicine, i.e. those who claim that the time accepted model of measure-treat-measure and “treatment” of the fundamental root of the “disease” is not clearly or regular practiced. Although to be fair, a very similar claim could be leveled at mainstream medicine, after all the culture of cut, burn or poison in cancer hardly “treats” the fundamental root of that disease either!
However it is in my mind, that we must keep nearer and dearer to our hearts the theories of aging, constantly looking out for that aging genesis, so that it may be controlled at its base/ beginning. Naturally we must continue to use the best tools that are available to us today, whether that be bio-identical hormone replacement, nootropics, methylation, chelation, stem cell therapy or RNA-i (add to this list as you see fit). But let us not lose sight that we need to adopt the means to measure aging itself through biological aging measurement, in order to justify and examine individual treatment methods. Ultimately we have to trigger the regenerative responses- to truly reverse and halt aging, rather than to be merely patching and slowing.
Keeping a close eye on the theories of aging and evaluating how antiaging medicine may be affecting their fundamental core(s) is a real scientific step on the road to an ageless (ergo disease free) society.
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