Aging-Clock Theory
According to the aging-clock theory of aging, aging is programmed into our bodies like a clock ticking away from the moment of conception. One of the best examples of an aging clock in humans is the menstrual cycle, which begins in adolescence and ends with menopause. The aging-clock theory is part of programmed aging, in which aging is seen as a normal part of a sequence leading from conception through development to senescence and finally to death.
One version of the aging-clock theory emphasizes the roles of the nervous and endocrine systems. This version postulates that aging is timed by a gland, perhaps the hypothalamus, the thymus, or the pituitary gland. Such a gland acts like an orchestra conductor or a pacemaker to regulate the sequence of physiological changes that occur over time. Some support for this idea comes from observations that the hormone dehydroepiandrosterone (DHEA) is found in higher levels among younger people. Experimenters have also discovered that DHEA supplements help laboratory rats live longer.
The aging-clock theory has encouraged research on the role of hormones secreted by the thyroid, pituitary, and thymus glands (Lamberts, van den Beld, & van der Lely, 1997). These include human growth hormone, which can now be manufactured in quantity through genetic engineering. In experiments, volunteers injected with growth hormone lost flabby tissue and grew back muscle, essentially reversing some manifestations of the aging process for a time. Other investigators are interested in hormones produced by the pineal gland, which may help regulate the “biological clock” that keeps time for the body.
Hormones and the endocrine system clearly play a major role in the process of aging. Hormones control growth, development, and reproduction in plants and animals. Biologists recognize a phenomenon here called semelparity. The best example is the Pacific salmon, which swims upstream to lay its eggs and then dies. So-called annual plants also exhibit semelparity: The tomato plant flourishes, produces fruit, and then dies away as the autumn leaves begin to fall.
But we find no comparable biological process in humans. We do recognize the profound age-related hormonal change of menopause, which comes with the loss of cells in the ovary that produce estrogen. Female mammals are born with a finite number of egg cells, so menopause is an example of a preprogrammed life event linked to age. Menopause is not a disease itself—it is, rather, a normal part of aging—but it is tied to health problems of aging because the loss of estrogen often weakens bone-mineral metabolism, resulting in thinner bone structure—a condition known as osteoporosis. Thin bones can lead to fractures, which in turn may compromise an older person’s ability to live independently.
Biogerontology continues to search for a “magic clock” that would give definitive knowledge of biomarkers to measure aging. Recently, scientists have begun to use artificial intelligence as a tool to chart aging at the deepest possible level (Zhavoronkov & Mamoshina, 2019).
Cross-Linkage Theory
Connective tissue in the body, such as the skin or the lens of the eye, loses elasticity with advancing age. We recognize the result as wrinkling of skin and cataracts. The explanation for this change lies in a substance known as collagen, a natural protein found in skin, bones, and tendons. According to the cross-linkage theory of aging, the changes we see result from the accumulation of cross-linking compounds in the collagen, which gradually become stiff. As in the waste accumulation theory, the piling up of harmful molecules is thought to eventually impair cell function. Some of this cross-linking may be caused by free radicals, which are cited in several theories of aging. Cross-linkage and collagen, therefore, are related to other changes in macromolecules and organ systems as they age (Bilder, 2016).
Free Radicals
Free radicals are unstable organic molecules that appear as a by-product of oxygen metabolism in cells (Armstrong et al., 1984). Free radicals are highly reactive and toxic when they come in contact with other cell structures, thus generating biologically abnormal molecules. The result may be mutations, damage to cell membranes, or damage by cross-linkage in collagen.
Free-radical damage has been related to many syndromes linked with aging, such as Alzheimer’s disease, Parkinson’s disease, cancer, stroke, heart disease, and arthritis. According to the free-radical theory of aging, damage created by free radicals eventually gives rise to the symptoms often associated with aging.
An important point about this theory is the fact that the body itself produces so-called antioxidant substances as a protection against free radicals. These antioxidants scavenge or destroy free radicals and thus prevent some of the damage to cell structures. The production of antioxidants is, in fact, correlated with the life span of many mammals.
Free-radical theory has prompted some observers to believe that consuming antioxidant substances, such as vitamin E, might slow down the process of aging. Genetic engineering techniques can now be used to produce antioxidants in vast quantities, but antioxidants are also supplied by the food we eat. Vitamins A, C, and E, as well as less familiar enzymes, play a role as antioxidants. Animal studies to date, however, show that consumption of antioxidants produces only minimal effects on aging.
Biologists recognize the importance of diet in longevity. It turns out that the dramatic doubling of human longevity, compared with other primates, could be understood in terms of inflammation. Inflammatory processes appear to have a role in conditions such atherosclerosis (buildup of plaques in arteries), Alzheimer’s, cancer, and diabetes. Gains in longevity may be understood in terms of reduced levels of inflammation. For that reason, an anti-inflammatory diet is the subject of important research today (Finch, 2007).
Cellular Theory
A major finding from cell biology is that normal body cells have finite potential to replicate and maintain their functional capacity. This potential appears to be intrinsic and preprogrammed, part of the genetic code. The cellular theory of aging argues that aging ultimately results from this progressive weakening of capacity for cell division, perhaps through exhaustion of the genetic material. That cellular limit, in turn, may be related to the maximum life span of species.
One of the major milestones in the contemporary biology of aging was the discovery that cells in laboratory culture have a fixed life span. Leonard Hayflick (1965) found that normal human cells in tissue culture go through a finite number of cell divisions and then stop. This maximum number of divisions is known as the Hayflick limit. Hayflick found that cells replicate themselves around 100 times if they are taken from fetal tissue. But if taken from a 70-year-old, they reach their limit of “aging” after 20 or 30 divisions.
Cells taken from older organisms divide proportionately fewer times than those taken from younger ones. Normal human cells that are frozen at a specific point in their process of replication and later thawed seem to “remember” the level of replication at which they were frozen. Furthermore, normal cells from a donor animal that are transplanted will not survive indefinitely in the new host.
Cell division in the laboratory sheds light on an interesting question: Can human bodies become immortal? The answer is yes, but there’s a catch. We have to get cancer to do it. The classic instance is the case of so-called HeLa cells—an immortal remnant of a terminally ill young woman named Henrietta Lacks (HeLa), who died in Baltimore in 1951 (Skloot, 2010). Before she died, a few cancerous cells were removed from her body and put into tissue culture: essentially, put down on a glass lab dish and supplied with cell nutrients. Scientists were surprised