June 19, 2018—(BRONX, NY)—Throughout the animal kingdom, smaller animals usually live longer than larger ones of the same species. A key reason for this longevity boost is that smaller animals typically have reduced activity of key growth factors, including insulin-like growth factor-1 (IGF-1). Signaling of this pathway is triggered when IGF-1 circulating in blood binds to IGF-1 receptors found on many types of cells in the body, resulting in growth-promoting effects on those cells.

In humans, raised IGF-1 levels are associated with increased risk for several types of cancer, including prostate, breast and colorectal cancer—while reductions in IGF-1’s influence have been linked to longevity. Engineering mice to have fewer IGF-1 receptors increases longevity in females; and studies from the Einstein Longevity Gene Project have similarly shown that many centenarians have diminished IGF-1 signaling due to genetic mutations in their IGF-1 receptors. Drugs that block IGF-1 receptors have been developed and tested in human cancer trials. Since such drugs muffle IGF-1 signaling, they could potentially help delay aging in the general population. But until now, no one has tested whether targeting this hormonal pathway can delay aging.

In a study published online on June 19 in Nature Communications, Derek M. Huffman, Ph.D., and colleagues extended the lives of female mice using a monoclonal antibody (mAb) that targeted their IGF-1 receptors, as a way to inhibit IGF-1 signaling. The study began with 18-month old male and female mice (equivalent in age to 50-60 year old people). These “older” mice received weekly injections of either the mAb or a control solution for the remainder of their lives and their age-related health outcomes and lifespan were monitored. Male mice injected with the mAb showed little improvement compared with male controls, but mAb-treated female mice fared much better with respect to lifespan and healthspan: Compared with female controls, the mAb-treated females had a median lifespan that was nine percent longer and they were also less likely to develop cancer; Remarkably, females receiving the drug had more youthful diastolic cardiac function, exercise tolerance, grip strength and motor coordination and had lower levels of pro-inflammatory proteins (cytokines and chemokines) that are associated with aging.

Importantly, these beneficial effects were achieved even though treatment wasn’t started until the mice were well past middle age. This suggests that mAbs targeting the IGF-1 receptor could eventually be optimized for use in older women to extend their lifespan and healthspan.

Dr. Huffman is an associate professor of molecular pharmacology and medicine, and co-director of the Chronobiosis and Energetics/Metabolism of Aging Core (CEAC) at Einstein.