Pharmaceutical Interventions into the Aging Process

The genetic manipulations used in the laboratory are not likely to be well received as therapeutic tools. Once the longevity extension mechanisms described above were identified, many scientists independently tried to develop pharmaceutical interventions by feeding various drugs suspected of regulating those two processes to their laboratory animals. Five of those experiments have shown signs of success. Although those independent experiments used different intervention strategies and administered different molecules to the laboratory animals, they all recorded significant increases in the animals' health span (comparable to those in Figure 1) and/or a significant extension of the animals' functional and mental abilities.

A recent experiment done by Kang et al. (2002) may serve as an example of this category of data. Those researchers fed a drug called 4-phenylbutyrate to fruit flies throughout all or part of their lives. This dietary pharmaceutical intervention resulted in a delayed onset of senescence in the treated flies, with survival curves similar to those shown in Figure 1. It turns out that this drug alters the manner in which DNA normally wraps itself around certain chromosomal proteins, in what appears to be an evolutionarily conserved manner (Hekimi and Guarente), and this alteration significantly changes the pattern of gene expression in the animal. Some genes are repressed, and others are enhanced. One of the genes most significantly enhanced is an ADS gene identical to that found to be highly effective in extending longevity in genetically engineered flies and worms. Thus, it is possible, although not yet proved, that this drug can bring about its longevity extension effects because it increases an animal's resistance to oxidative stress. Another interesting observation from this experiment is the fact that different strains of flies needed different drug doses to yield the same result. This implies the existence of genetically based individual differences in the response to drug-based longevity interventions. No reports are available regarding the existence of various side effects or trade-offs in any of these experiments.

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