FURIN Stimulates NOTCH2 and NOTCH3 Pathways Leading to Return of Function in Aged Muscle Cells

Background: People have been looking for the basic genetic mechanism of aging for as long as we have known about molecular biology. Here we present a study where we were able to identify the root cause of aging and by stimulating the Notch2, and Notch3 pathways with FURIN we were able to return function to aged muscles cells. Sarcopenia is known to affect older humans. Methods In silica, analysis of skin, muscle, neurons and macrophages were examined to find molecules that were progressively up or down regulated across decades of life. In this way we identified loss of FURIN as a putative root cause of aging. We then used a well-documented model of muscle cell aging and transfected the cells with a FURIN plasmid. We examined the FURIN levels and cellular function. Results Aging muscle cells lose their ability to form myotubes, a necessary step in muscle repair. Expression of Furin in aged muscle cells leads to decreased GZMB levels, an increase in embryonic MyHC and IGF-1 levels, restores myogenic potential and the ability to form myotubesmyotubes. Conclusions: FURIN was able to restore aged cells ability to fuse into functional myotubes. This may be applicable to other consequences of aging as we saw in skin cells in our in silica experiments. This finding may point us toward a way to reverse some of the effects of aging in humans.