Testing drug combinations to slow aging.

Aging is a complex multifactorial process, meaning that multiple pathways need to be targeted to effectively prevent or slow aging [1]. A number of molecular pathways are well known for influencing aging, but only a few have been successfully targeted with individual drugs, and these drugs do not individually target all aging pathways. However, combinations of these drugs might have the potential of effectively broadening the scope of aging targets. There are a number of drug combinations that could be combined based on different but overlapping pharmacological activities. Since the number one criterion for selecting drugs should be based on known anti-aging effects, for example, in preclinical mouse studies, the number of drugs available to consider is markedly reduced. Three drugs with well-validated anti-aging effects in laboratory animals, rapamycin [2,3], acarbose [4], and SS31 [5,6], are well suited to therapeutic multiplexing as a way to enhance healthy aging and stop the development of lesions associated with aging and physiological dysfunction based on interactive cellular mechanisms of each drug. The inter-drug relationship of these three drugs can easily be perceived by explicitly defining the mechanism of action of each drug and how it overlaps and extends the mechanism of action of each of the other drugs in the complex. A plausible explanation then of how they could act as a multiplex in targeting molecular pathways in aged mice is as follows: