How can we slow or even halt the steady march of aging? In a previous post, I reviewed a paper that asked “What causes aging?” (the prevailing hypothesis is that aging is caused by accumulating cell damage). Understanding why we age is important for developing ways to interfere with the process. But there are other ways to study aging in the hopes of one day developing the mythical “elixir of life”. A recent fruit fly paper published in Cell Reports by the Walker lab instead asked, “How does caloric restriction increase lifespan?”
Scientists discovered a long time ago that caloric restriction can extend lifespan in a wide range of animal models, including rats and fruit flies. But the diet is severe and leads to side effects including reduced energy levels and sensitivity to cold. Who wants to live longer in such misery? Decreased food intake itself can’t be the cause of increased lifespan (it does seem rather counterintuitive), so what is going on?
The authors found that activating a molecule called AMPK could increase lifespan just like dietary restriction, without all those miserable side effects. Normally, AMPK is activated when a cell needs more energy (such as when the animal isn’t eating enough calories). AMPK then triggers a process called macroautophagy, which means that components and molecules inside of cells are broken down and recycled for energy. This usually happens when the cell needs more energy than it is being provided, and the first things to go are old, unnecessary, and damaged cellular components. By artificially activating AMPK, the authors tricked the cells into breaking down more of this “cellular garbage”, slowing the accumulation of damage that leads to aging.
Perhaps the most exciting finding was that the authors could extend the lifespan of adult flies just by activating AMPK in the intestines. This manipulation slowed aging not just in intestinal cells, but also in brain tissue and even muscles. In fact, older flies even showed improved climbing ability. Although there is much work left to be done, these findings give hope that one day, aging can be slowed in adult humans just by swallowing a pill that activates AMPK in our gut.
- Ulgherait M., Michael Rera, Jacqueline Graniel & David W. Walker (2014). AMPK Modulates Tissue and Organismal Aging in a Non-Cell-Autonomous Manner, Cell Reports, 8 (6) 1767-1780. DOI: http://dx.doi.org/10.1016/j.celrep.2014.08.006