Aging interventions get human

Over the last three decades, aging research has made great strides. At least in non-vertebrate animal models such as yeast and worms, it is possible to extend lifespan through reduced or ablated expression of hundreds of genes. The number of genes tested in mice are substantially less but the data so far is consistent with modulation of aging by numerous genes and pathways. More importantly, evidence exists that many of these genetic interventions extend healthspan and protect against the onset of age-associated chronic diseases. Recently, small molecules have entered center stage, with both natural products and clinically approved compounds reported to delay aging [1]. These findings raise the question of whether it is possible to forestall aging as an approach to maintain vitality and delay the onset of multiple chronic diseases simultaneously. However, there are significant hurdles to testing human aging drugs and many have been skeptical that aging interventions will ever enter the clinic. Among the foremost challenges, aging is not formally considered a disease by the FDA and the prospects of testing whether drugs extend human lifespan directly promises to be a long and exorbitantly expensive process. There is also the challenge of performing clinical trials in aging individuals who are still generally healthy. Foremost among these is the extra level of safety that will need to be incorporated since care must be taken not to do harm to healthy, older people. One potential solution is to test compounds against deleterious phenotypes associated with human aging-but which compound and which phenotype? This question has been debated extensively. Sometimes the best approach is to start testing and let the results dictate the path forward. In this vein, Mannick et al. recently reported the results of the first human aging trial [2]. They chose a first generation derivative of the drug rapamycin (known as everolimus or RAD001), which has been shown to extend lifespan in all four major animal models of aging: yeast, worms, flies and mice [1]. Importantly, rapamycin, which is a direct inhibitor of the mTOR kinase, can extend lifespan by 25% in mice and even show efficacy when initiated in 20 month old mice [3, 4]. Most studies indicate that rapamycin extends healthspan as well [1]. Rapalogs, or rapamycin derivatives, are approved for treatment of several disease indications, but also have a range of side effects. Mannick et al. chose to administer RAD001 to healthy people 65 …