Toward sirtuin activators in the clinic

Lenny Guarente is on the warpath lately, with three recent reviews about the therapeutic potential of drugs that target sirtuins:

• Sirtuins as potential targets for metabolic syndrome
• SIR2: a potential target for calorie restriction mimetics (with D. Chen)
• Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction (with C. Haigis)

Taken together, these reviews address an issue relevant to the development of anti-aging medicine: Given the current regulatory laws in the US and elsewhere, getting drugs approved as anti-aging therapies per se is difficult to say the least, approaching the level of practical impossibility. Beyond the political and sociological challenges of defining aging as a pathology in itself are a huge number of nuts-and-bolts issues: How does one measure successful delays in aging? How does one define a Phase I (or II, or III) population, and secure subject compliance over the relevant timescales?

But suppose compounds with anti-aging properties (to be more precise, I should say, “compounds that target pathways known to modulate lifespan in experimental organisms”) are approved for clinical treatment of acute or shorter-term chronic diseases, where the trial populations and standards for efficacy are easier to define. We’d then have anti-aging drugs ready for off-label use after they’ve been proven effective for their on-label purpose. (And since the drugs will be employed prophylactically against the metabolic syndrome, they would have also been carefully vetted for their long-term safety.)

So even if the language used by those involved in developing the products might not always explicitly say so, these are the first steps toward a bona fide anti-aging pharmacopoiea.