Complications in Developing Drugs to Slow Aging

Trying to safely slow down aging, usually by developing drugs to replicate some of the metabolic and epigenetic alterations caused by calorie restriction or exercise, is an immensely complicated undertaking. Success will be slow in coming, and the end result will be of little use for those already old - so other than an increase in the understanding of how metabolism and aging relate to one another, we should not expect this field of research to contribute much to the bottom line of our own longevity.

Nonetheless, this is the mainstream of research into longevity science and where most of the money goes. That state of affairs will have to change in favor of a focus on the more practical path of repairing biochemical damage associated with aging, with the aim of creating biotechnologies that can reverse the root causes of aging and thus bring about some degree of rejuvenation.

Here is an example of the sort of complications that arise when attempting to adjust metabolism. Interventions that are beneficial at one point in life may be harmful at others, and may further interact poorly with one another to produce a net harmful effect even though they are individually beneficial:

We tested the effects of a Class I histone deacetylase inhibitor (HDAcI) (sodium butyrate, NaBu) on the longevity of normal- and long-lived strains of Drosophila melanogaster. We report that this HDAcI has mixed effects in the normal-lived Ra strain in that it decreases mortality rates and increases longevity when administered in the transition or senescent spans, but decreases longevity when administered over the health span only or over the entire adult lifespan. It has dose-dependent effects when administered over the entire larval+adult life span. Only deleterious effects are noted when administered by either method to the long-lived La strain.

This apparently contradictory set of results is, however, what would be expected if the gene regulatory mechanisms affected by NaBu were those intimately involved in inducing gene expression patterns characteristic of a healthy senescence. Thus "mid- to late-life" drugs may have different stage-specific effects on different genomes of a model organism. A different HDAcI (suberoylanilide hydroxamic acid, SAHA) administered to the normal-lived strain showed similar late-life extending effects, suggesting that this is not an isolated effect of one drug.



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