Table 1. Some Important Theories of Aging.

It should be emphasized that these theories should not be seen as competing but as complementary.

Theory	Premise
“Wear and tear” theory	Dr. August Weismann, a German biologist, proposed in 1881 that the body and its cells are worn down by toxins in our diet and environment; by the excessive consumption of fat, sugar, caffeine, alcohol and nicotine; by the ultra-violet rays of the sun; and by the many other chemical, physical and emotional stresses to which we are routinely exposed (reviewed by (Kirkwood and Cremer 1982)). Moreover, with age, the body gradually loses its ability to repair associated damage, thus rendering older individuals more susceptible to disease. “The neuroendocrine theory”, developed by Vladimir Dilman, Ph.D., elaborates on the “wear and tear” theory by focusing on the neuroendocrine system. It suggests that as we age, the body produces lower levels of hormones resulting in catastrophic effects on normal physiology, such as muscle atrophy and poor recovery from injury or illness (Dilman et al. 1986).
Hayflick limit (or “aging clock”) theory	In 1961, Drs. Leonard Hayflick and Paul Moorhead discovered that human fibroblasts (from lung, skin, muscle, heart) can only divide a finite number of times in culture (Hayflick and Moorhead 1961). Dr. Hayflick also noted that, as these cells approached the end of their division limit, they acquired attributes commonly associated with old tissue, such as the destruction of their cellular structure, reduced capacity to produce energy or synthesize enzymes, and an intracellular buildup of waste materials. Dr. Hayflick concluded that these changes play a central role in the manifestation of aging, and result in the death of the individual well before all of its cells fail to divide. Arising from Hayflick’s findings was the “waste accumulation theory”, which postulated that cells produce more waste (e.g. toxins) than they can properly eliminate in the course of their life time, culminating in dysfunction and death. Many theories have been put forth to explain how Hayflick’s limit (i.e. replicative senescence) is ultimately expressed in cells, and evidence clearly indicates a critical role for telomerase, a protein that maintains the caps of chromosome ends, in dictating replicative life span (i.e. the telomerase theory of aging) (Holt et al. 1996).
Genetic control theory	We are each born with a distinctive genetic code. i.e. our DNA blue-print. The “genetic control theory” proposes that each individual harbors a predetermined tendency to certain types of physical and mental functioning and that genetic inheritance plays a major role in determining how quickly we age and how long we live.
Error catastrophe theory	In 1963, Dr. Leslie Orgel wrote that because the “machinery for making protein in cells is so essential, an error in that machinery could be catastrophic (ORGEL 1963).” In particular, the production of proteins and the duplication of DNA are not always carried out with perfect accuracy. Since protective systems are occasionally “error-prone”, the gradual accumulation of flawed molecules has been proposed to cause disease and other age-related changes. This theory differed slightly from the “somatic mutation theory” proposed by Dr. Leó Szilárd in 1959, in that it postulated an error in information transfer from sites other than just DNA (Szilard 1959).
Free-radical theory	One of the most popular theories of aging, first proposed by Dr. Denham Harman in 1956, is the “free radical theory of aging (Harman 1956).” This theory postulates that aging results from the gradual accumulation of cellular damage caused by reactions with highly reactive molecules known as “free radicals.” Free radicals (or reactive oxygen or nitrogen species) are produced endogenously via normal metabolic processes or upon exposure to numerous exogenous agents, including ionizing radiation and cigarette smoke. Since mitochondria are responsible for manufacturing chemical energy and creating harmful free radicals, the constituents of this organelle (namely DNA) are the major sites for oxidative reactions. The “mitochondrial theory”, developed by Dr. Harman in 1972, postulates that mitochondrial decay, in particular, results in impaired energy generation and dysfunctional cellular activity that gives rise to age-associated pathologies like skeletal muscular and neurological degeneration, heart failure, strokes, other diseases, and death (Harman 1972). Although not related to the “oxidative” theories above, the “cross-linkage theory” implicates another endogenous agent, i.e. crosslinking agents, in the formation of covalent bridges between macromolecules (e.g. proteins and nucleic acids) that effect cellular dysfunction and ultimately death.
Auto-immune theory	The autoimmune theory, proposed by Dr. Roy Walford in 1964, hypothesizes that two types of white blood cells of the immune system (i.e. B and T cells) weaken with age, and malfunction (Walford 1964). B cells lose their vigor in attacking bacteria, viruses, and cancer cells, and T cells lose their capacity to attack cells foreign to the body. These changes render the individual more prone to infections and tissue damage, which may ultimately cause death. Additionally, as the system breaks down, the body is more apt to have autoimmune reactions, in which the body’s own cells are mistaken for foreign material and are destroyed or damaged by the immune system.