MyMD-1 improves health span and prolongs lifespan in old mice: A non-inferiority study to rapamycin.

Aging and age-related diseases represent a compelling therapeutic goal for senolytics and drugs targeting inflammatory or metabolic pathways. We compared MyMD-1, a synthetic derivative of the alkaloid myosmine capable of suppressing TNF-α production, to rapamycin, the best characterized drug endowed with anti-aging properties. In vivo, a longitudinal cohort of 54 C57BL/6 mice, 19-month-old at the start, was randomized to receive MyMD-1, high-dose (126 ppm) rapamycin, or low-dose (14 ppm) rapamycin plus metformin. Each treatment arm included 18 mice (10 females and 8 males) and was followed for 16 months or until death. Lifespan was significantly longer in MyMD-1 than rapamycin (P= 0.019 versus high-dose and 0.01 versus low-dose) in a Cox survival model that accounted for sex and serum levels of IL-6, TNF-α, and IL-17A. MyMD-1 also improved several health span characteristics, resulting in milder body weight loss, greater muscle strength, and slower progression to frailty. In vitro, MyMD-1 and rapamycin were compared using a panel of 12 human primary cell systems (BioMAP Diversity PLUS™) where a total of 148 biomarkers are measured. MyMD-1 possessed anti-proliferative, anti-inflammatory, and anti-fibrotic properties. Many were shared with rapamycin, but MyMD-1 was more active in the inhibition of pro-inflammatory and pro-fibrotic biomarkers. Overall, MyMD-1 emerges as a new compound that, even when begun at an advanced age, induces beneficial effects on health and lifespan by modulating inflammation and tissue remodeling.