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Anti-aging Drugs, Metabolism, and Disease

17 November, 2007 - 2 min read

Since today is my birthday I find myself thinking about aging. I went back and listened to one of the first FIB podcasts. It features Leonard Guarente, who helped start Elixir pharmaceuticals, a company specifically targeting aging and metabolic disease. Here’s a link to the mp3.

Is aging just a disease? Metabolism and aging appear to be very tightly coupled. Even more interesting is how calorie restriction (starvation) has a direct impact on reproduction and lifespan. Dr. Leonard Guarente identified the SIR2 gene 6 or 7 years ago. Sirtuin enzymes (pictured above) are NAD-dependent and activated under special conditions like starvation. The biochemistry suggests that therapies could be possible. Knockout the SIRT1 gene in mice and the quality of life is greatly decreased. Starve any organism from yeast to chimps and they live longer by activating specific pathways. There’s 7 genes in mammals so there’s obviously much left to be understood. Trying to inhibit specific enzymes is pretty common, but targeting pathways and complex signaling in cellular metabolism can be tricky. The signals exist in nature. The technology developed in systems biology and metabolomics could really help answer some important questions in the next 10 years or so.

Avalon pharmaceuticals has a technology for generating pathway signatures, so rather than screening compounds against a single target they claim to be able to target entire pathways. They also have an advanced candidate for solid tumor cancers that’s an IMPDH inhibitor. IMPDH is another NAD-dependent enzyme that I have done a small amount of work on.