IL-11 inhibition by anti-aging drugs in mice: sex-specific effects for perigonadal fat depots

Many drugs that extend mouse lifespan do so only in male mice, for reasons unknown. Recent work has shown that aging leads to increases in IL-11, a pro-inflammatory cytokine, and that inhibiting IL-11 effects can increase mouse lifespan. Here we report effects of seven male-specific anti-aging drugs on IL-11 levels in aged mice (canagliflozin, epicatechin, mitoglitazone, astaxanthin, meclizine, halofuginone, and 16-OH-estradiol). None of the drugs altered IL-11 in liver. All seven led to declines in IL-11 in inguinal (i.e. subcutaneous) fat, in both male and female mice. In contrast, in perigonadal (i.e. intra-abdominal) fat five of the seven drugs showed a sex-specific effect, decreasing IL-11 in males while increasing it in females. The other two, astaxanthin and meclizine, did not produce significant changes in perigonadal IL-11 in either sex. Sex-specific differences in IL-11 production in abdominal fat depots may contribute to sex-specific lifespan increases in drug-treated mice.