Development of novel oral drug aiming at disease-free aging

The most devastating aspect of aging is debilitating morbidity associated with it. This is a result of a decline in proper operation of key quality-control system called autophagy that in case of mitochondrial-recycling, it is called mitophagy. It ensures removal of damaged intracellular organelles and their replacement by newly formed ones. Aging-associated malfunctioning of it result in morbidities such as Alzheimer`s disease, Parkinson`s disease, congestive heart failure and skeletal muscle weakness.

Spermidine (Spd) is a natural product able to promote longevity via the induction of autophagy and mitophagy. However, Spd can be rapidly metabolized by gut bacteria and human cells, resulting in unfavorable products. Preliminary studies that we conducted with a subset of Spd derivatives identified a compound with superior potency compared to that of Spd, with respect to enhanced mitophagy, protection against oxidative-stress damage, organismal longevity and vitality. We took advantage of the model organism C. elegans to pin-point the cellular and molecular mechanism by which tested molecules are operating. The objective of our research is to take advantage of our initial achievements and conduct further structural optimization in order to generate a novel drug that can effectively treat degenerative diseases associated with aging.