The major theories of aging as a consequence of random events are:

Cross-linking
Wear and Tear
Free Radical
Rate of Living
Somatic Mutations

The cross-linking theory of aging is based on the observation that with age, our proteins, DNA and other structural molecules develop inappropriate attachments or cross-links to one another. These unnecessary links or bonds decrease the mobility or elasticity of proteins and other molecules. Proteins that are damaged or no longer needed are normally broken down by enzymes called proteases, and the presence of cross-linkages inhibits the activity of proteases. These damaged and unneeded proteins, therefore, stick around and can cause problems.

Some research supports this theory. Cross-linking of the skin protein collagen has been shown to be at least partly responsible for wrinkling and other age-related changes in skin. Cross-linking of proteins in the lens of the eye is also believed to play a role in age-related cataract formation. Researchers speculate that cross-linking of proteins in the walls of arteries or the filtering systems of the kidney account for at least some of the atherosclerosis (once called hardening of the arteries) and age-related decline in kidney function observed in older adults.¹ Another study conducted at the Bjorksten Institute in Wisconsin treated brain tissue from young animals with known cross-link-inducing compounds. That brain tissue soon looked quite similar to older brain tissue with its naturally cross-linked brain proteins, adding evidence in support of this theory of aging.²

Many scientists agree that cross-linking of proteins, and perhaps the cross-linking of DNA molecules as well, are components of aging, the lack of other direct experimental evidence at this time leaves many unconvinced that it is a primary cause of aging.

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The wear and tear theory of aging suggests that years of damage to cells, tissues and organs eventually wears them out, killing them and then the body. The damage begins at the level of molecules within our cells. The DNA that makes up our genes sustains repeated damage from toxins, radiation and ultraviolet light. Our bodies have the capacity to repair DNA damage but not all of those repairs are accurate or complete. Thus the damage progressively accumulates. Our mitochondria, the tiny "powerhouses" inside our cells that transform energy into useful form, are also susceptible to accumulated errors, and they have only a small capacity for repair.

Evidence to support the wear and tear theory of aging comes from insect observations. For example, few cells in the wing muscles of adult fruit fly reproduce, and while week-old fruit flies can fly 110 minutes without landing, month-old fruit flies must land after 19 minutes. Additional evidence comes from the accumulation of mitochondrial damage with aging in some insects. However, scientists point out that this wear and tear could easily be viewed as a result of aging and not a cause of it.³ Another argument against wear and tear as a major cause of aging is the fact that while some investigators report an age-related decline in the ability of certain animals (beagles, mice and rats) to repair their damaged or worn DNA, other scientists, studying beagles, mice and hamsters did not observe such a decline.⁴

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Proponents of the free radical theory of aging, among them Denham Harman of the University of Nebraska,⁵ note that free radicals can cause DNA damage, the cross-linking of proteins⁶ and the formation of age pigments. They also point to the fact that antioxidants, which oppose the toxic free radicals, have been shown, when given in large quantities to laboratory animals, to slow some aging processes.⁷ Some researchers have suggested, however, that such animals, when fed large quantities of antioxidants, decrease their total calorie intake significantly. And caloric restriction is the only intervention actually proven to increase life span in animals. It could be argued that the benefits derive not from the action of the antioxidants, but from the appetite suppression they apparently induce.⁸

Many scientists focus on the specific effects of free radicals on mitochondria, the tiny powerhouses of our cells that transform energy into useful forms. Since mitochondria have little capacity to repair themselves when they are damaged, free radicals can cause much irreversible damage.^9,10 Other researchers point out that although mitochondria do indeed suffer damage from free radicals, that damage seldom triggers wholesale cell death.¹¹ The connection between free radical damage to the mitochondria and the broader aging process remain unclear.

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Arguing against the rate of living theory of aging is the fact that those humans who live to be 100 have taken more breaths, had more heartbeats and metabolized more oxygen than the longest-lived animals. And centenarians are as likely to have lived physically active lives as sedentary ones. Thus the rate of living theory has less evidence to support it than other theories.

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One argument against the somatic mutation theory comes from observations of inbred animals. In theory, inbreeding should magnify the effects of mutations. Animals with deleterious mutations bred to others with the same deleterious mutations should produce offspring that die off faster, while inbred animals with helpful mutations should live longer. In fact, virtually all inbred animals have shorter life spans when compared to outbred animals.

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