LAUSR

“Targeting signs of aging”. It sounds more like a punch-line of a TV commercial, than a consequence of fundamental science. But as we observed recently, it might actually be possible to achieve just that, using a prospectively designed FOXO4-p53 interfering peptide that targets so-called “senescent” cells [1]. More research is needed to fully assess its true translational potential and whether it is even safe to remove such cells. However, these findings pose a very attractive starting point to develop ways to live out our final years in better health. Aging has often been considered as an integral part of life; a form of “noise” that cannot be targeted or tampered with. This is in part because for long the underlying causes of organismal aging were simply too elusive to comprehend, let alone modify. The chronic build-up of DNA damage has now evidently been established as a major cause for aging, but to counteract the genomic damage that has occurred over a lifetime is an entirely different challenge altogether [2]. One approach to overcome this issue, is to eliminate those cells that are too damaged to faithfully perform their duty and to replace them by fresh and healthy counterparts. Senescent cells are exciting candidates for such an approach. Comparable to formation of rust on old equipment, like a bicycle (Figure 1), they accumulate during aging and especially at sites of pathology. They develop a chronic secretory profile that is thought to impair tissue renewal and contribute to disease development, for instance by keeping neighboring cells “locked” in a permanent state of stemness [2]. Senescence can be beneficial in a transient setting, but the genetic removal of senescent cells over a prolonged period of time was found to be safe and to potently extended healthand lifespan of naturally aging mice [3]. Thus, senescence is an established cause for aging and targeting them is warranted. But can they also be eliminated therapeutically? And are such methods then safe on their own? And last, but not least, would such methods be applicable to not merely delay, but also to reverse aging?