| First Author | Jergović M | Year | 2021 |
| Journal | Geroscience | Volume | 43 |
| Issue | 2 | Pages | 539-549 |
| PubMed ID | 33629207 | Mgi Jnum | J:328217 |
| Mgi Id | MGI:6881673 | Doi | 10.1007/s11357-021-00343-z |
| Citation | Jergovic M, et al. (2021) IL-6 can singlehandedly drive many features of frailty in mice. Geroscience 43(2):539-549 |
| abstractText | Frailty is a geriatric syndrome characterized by age-related declines in function and reserve resulting in increased vulnerability to stressors. The most consistent laboratory finding in frail subjects is elevation of serum IL-6, but it is unclear whether IL-6 is a causal driver of frailty. Here, we characterize a new mouse model of inducible IL-6 expression (IL-6(TET-ON/+) mice) following administration of doxycycline (Dox) in food. In this model, IL-6 induction was Dox dose-dependent. The Dox dose that increased IL-6 levels to those observed in frail old mice directly led to an increase in frailty index, decrease in grip strength, and disrupted muscle mitochondrial homeostasis. Littermate mice lacking the knock-in construct failed to exhibit frailty after Dox feeding. Both naturally old mice and young Dox-induced IL-6(TET-ON/+) mice exhibited increased IL-6 levels in sera and spleen homogenates but not in other tissues. Moreover, Dox-induced IL-6(TET-ON/+) mice exhibited selective elevation in IL-6 but not in other cytokines. Finally, bone marrow chimera and splenectomy experiments demonstrated that non-hematopoietic cells are the key source of IL-6 in our model. We conclude that elevated IL-6 serum levels directly drive age-related frailty, possibly via mitochondrial mechanisms. |
