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A More Unified Theory of Aging: Implications for Increasing Healthy Life Span

A.D.N.J. de Grey, B.N. Ames, J.K. Andersen, A. Bartke, J. Campisi, C.B. Heward, R.J.M. McCarter, G. Stock

Department of Genetics, University of Cambridge Cambridge, UK Department of Biochemistry and Molecular Biology, University of California, Berkeley, California USA; Buck Institute for Aging Research, Novato, California USA; Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California USA; Kronos Longevity Research Institute, Phoenix, Arizona USA; Department of Physiology, University of Texas Health Sciences Center, San Antonio, Texas USA; Department of Neuropsychiatry and Biobehavior, University of California, Los Angeles, California USA.

Aging is a three-stage process of metabolism, damage and pathology. Metabolism, the biochemical processes that sustain life, often generates toxins as byproducts. These toxins cause various types of damage, which may accumulate because they cannot be repaired by the body. Accumulating damage eventually causes age-related degeneration or pathology.

In an effort to understand aging, researchers have often tried to determine which processes in each of the three categories are the most important. For instance, they have tried to determine which metabolic processes have the greatest effect on the rate of damage accumulation or which types of damage have the greatest effect on the rate of accumulation of pathology. This has not been very successful, and researchers still disagree about which processes matter most. It may be better to design ways to delay all such processes.

All three stages of the aging process can be changed to some degree, but interventions do not always delay aging. Interventions that alter metabolism focus on slowing the rate at which metabolism causes damage. This approach can only modestly postpone pathology, because it is difficult to markedly change metabolism without redesigning basic life processes.

Interventions in pathology are also often ineffective. Interventions at this stage of aging are directed toward keeping people in better health longer. This eventually becomes impossible if the damage that causes the pathology continues to accumulate. By contrast, interventions designed to remove or repair accumulating damage sever the link between metabolism and pathology. Thus, intervention at this stage of the aging process can potentially postpone aging much more dramatically.

The major obstacle to changing the aging process by removing or repairing damage is that it requires substantially more sophisticated technology than either of the other approaches. We believe, however, that anti-aging medicine has progressed to the point where we now have within our reach many techniques that can make it possible for us to reverse damage. By reversing the damage as rapidly as it occurs, we could completely uncouple metabolism from pathology and eliminate the process of aging. While achieving this is a lofty goal, the potential effects of it, both on individuals and on society as a whole, must be seriously considered.

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