Research into sirtuins in relation to longevity has consumed a great deal of money over the past decade, more than enough to fully implement the Strategies for Engineered Negligible Senescence in mice, and yet there is very little to show for it aside from an increased knowledge of one small area of metabolism in a range of species. A drug to slightly slow the pace of aging in humans might yet result in the future, but if it does emerge then it is unlikely to provide greater benefit than, say, the practice of calorie restriction.
This is absolutely characteristic of present mainstream research into interventions in aging: expensive, slow, unlikely to produce results, and the plausible future outcomes if successful will be of limited benefit. Yet so much money has flowed into work on sirtuins that it has inertia now: research and attempts at development will continue until someone finds a way to shoehorn sirtuin activating drugs into a marginal therapy for something. This is a great pity: there are far better ways forward, more productive research plans for therapies to treat aging and age-related disease.
Here is a familiar refrain on sirtuins, nothing that we haven't heard before: a combination of interesting new details on metabolism relating to sirtuins and beating the drum with promises of future treatments under the implicit assumption of further funding for present research.
A gene called SIRT1, previously shown to protect against diseases of aging, plays a key role in controlling circadian rhythms. [Researchers] found that circadian function decays with aging in normal mice, and that boosting their SIRT1 levels in the brain could prevent this decay. Conversely, loss of SIRT1 function impairs circadian control in young mice, mimicking what happens in normal aging. Since the SIRT1 protein itself was found to decline with aging in the normal mice, the findings suggest that drugs that enhance SIRT1 activity in humans could have widespread health benefits. "If we could keep SIRT1 as active as possible as we get older, then we'd be able to retard aging in the central clock in the brain, and health benefits would radiate from that."
[Researchers] created genetically engineered mice that produce different amounts of SIRT1 in the brain. One group of mice had normal SIRT1 levels, another had no SIRT1, and two groups had extra SIRT1 - either twice or 10 times as much as normal. Mice lacking SIRT1 had slightly longer circadian cycles (23.9 hours) than normal mice (23.6 hours), and mice with a 10-fold increase in SIRT1 had shorter cycles (23.1 hours). In mice with normal SIRT1 levels, the researchers confirmed previous findings that when the 12-hour light/dark cycle is interrupted, younger mice readjust their circadian cycles much more easily than older ones. However, they showed for the first time that mice with extra SIRT1 do not suffer the same decline in circadian control as they age.
"I think we should look at every aspect of the machinery of the circadian clock in the brain, and any intervention that can maintain that machinery with aging ought to be good. One entry point would be SIRT1, because we've shown in mice that genetic maintenance of SIRT1 helps maintain circadian function." Some SIRT1 activators are now being tested against diabetes, inflammation and other diseases, but they are not designed to cross the blood-brain barrier and would likely not be able to reach the [suprachiasmatic nucleus that controls circadian cycles]. However, [researchers believe] it could be possible to design SIRT1 activators that can get into the brain.