Biochemical and cellular mechanisms of aging and degenerative disease: excessive, poor-quality caloric intake may deplete essential nutrients and interfere with cellular processes to produce degenerative damage.

It has long been known that caloric restriction retards aging and many degenerative disease processes. Various experiments have confirmed that caloric restriction enables animals' organelles and cells to retain their structural integrity into old age, in contrast to ad libitum counterparts. Calorically restricted animals also maintain greatly enhanced immune and DNA repair systems, handle outside threats-infectious agents, toxins, radiation, extreme temperatures-more proficiently, and usually avoid or defer the onset of cancers. But how caloric restriction works to achieve these remarkable results has so far eluded us. Our hypothesis suggests that the key to understanding how caloric and nutrient levels can influence so many physiological functions is to perceive food intake not only as a means of nourishing and strengthening the organism, but also as an environmental challenge. The organism's biochemical responses to excessive, particularly poor-quality, calorie intake, like its responses to other environmental threats, can potentially deplete essential nutrients, interfere with biochemical and cellular mechanisms, and produce degenerative damage. This chain of events occurs not only in animals in caloric restriction experiments, but also in virtually all organisms as they respond to chronic or high-level environmental challenges or receive inadequate nutrition. Because they cannot avoid these challenges, consume precise levels of nutrients required to deal with ongoing metabolic functions and outside threats, and do not function physiologically with total efficiency, all organisms incur degenerative damage, essentially every day, promoting aging and leading to various degenerative disorders.