Identifying new targets to help reduce age-related inflammation and frailty

Researchers exploring possible treatments for frailty and other age-related conditions have noted that chronic inflammation often accompanies aging and age-related diseases. In a study published in Proceedings of the National Academy of Sciences of the United States of America, Mayo Clinic researchers present data suggesting that inhibiting key cellular pathways may be an effective way to reduce age-related inflammation and frailty.

According to Mayo researchers, the enzyme family known as Janus kinase (JAK) plays an important role in senescence-related inflammation and frailty. Senescent cells accumulate with age and produce proinflammatory chemokines and cytokines, and extracellular matrix remodeling proteases, which comprise the senescence-associated secretory phenotype (SASP).

Mayo researchers observed that conditioned medium from senescent human preadipocytes induced macrophage migration in vitro and inflammation in healthy adipose cells and tissue. When the conditioned medium was derived from senescent cells treated with JAK inhibitors, the resulting medium was much less proinflammatory.

"The JAK pathway is activated in adipose tissue with aging, and inhibiting the JAK pathway in senescent cells effectively suppressed the SASP," explains one of the study's lead authors, Nathan K. LeBrasseur, M.S., Ph.D., co-chair of research in Physical Medicine and Rehabilitation at Mayo Clinic's campus in Rochester, Minnesota.

Mayo researchers also found that JAK inhibitors reduced inflammatory mediators in mice. Researchers examined aged mice, equivalent to 80-year-old people, before and after 10 weeks of treatment with JAK inhibitors. Administration of JAK inhibitors alleviated adipose tissue and systemic inflammation, and induced substantial improvement in physical function, including grip strength, endurance and physical activity.

"We speculate that targeting the SASP with interventions such as JAK inhibitors may alleviate frailty, and that this approach may also hold promise for treating other aging-related conditions," says Dr. LeBrasseur.

For more information

Xu M, et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proceedings of the National Academy of Sciences of the United States of America. 2015;112:e6301.