{"id":197822,"date":"2024-10-17T03:47:53","date_gmt":"2024-10-17T08:47:53","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2024\/10\/inhibition-of-il-11-signalling-extends-mammalian-healthspan-and-lifespan"},"modified":"2024-10-17T03:47:53","modified_gmt":"2024-10-17T08:47:53","slug":"inhibition-of-il-11-signalling-extends-mammalian-healthspan-and-lifespan","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2024\/10\/inhibition-of-il-11-signalling-extends-mammalian-healthspan-and-lifespan","title":{"rendered":"Inhibition of IL-11 signalling extends mammalian healthspan and lifespan"},"content":{"rendered":"

<\/a><\/p>\n

To support the data generated in Il11ra1<\/em>-deleted mice on a mixed C57BL6\/129 genetic background30<\/a><\/sup> and to more deeply dissect age-related effects, we studied young (3-month-old) and aged (2-year-old) female mice with deletion of Il11 (Il11<\/em>\u2212\/\u2212<\/em><\/sup>) on a C57BL6\/J background31<\/a><\/sup>.<\/p>\n

Immunoblots confirmed IL-11 up-regulation across tissues in old age in this additional strain (Fig. 1m<\/a>). Old female Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice had lower body weights and fat mass and preserved lean mass (Fig. 2a\u2013c<\/a>). The frailty score15<\/a><\/sup> of old female Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice was lower than that of old wild-type mice and their body temperatures were mildly increased (Fig. 2d<\/a> and Extended Data Fig. 5a<\/a>). Lower frailty scores were largely driven by improvements in tremor, loss of fur colour, gait disorders and vestibular disturbance (Supplementary Table 1<\/a>). Muscle strength was higher in both young and old Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice (a phenomenon that was observed for some other phenotypes) compared with age-matched controls (Fig. 2e<\/a> and Extended Data Fig. 5b<\/a>).<\/p>\n

Chronic inhibition of mTORC1 with rapamycin can cause glucose intolerance owing to indirect inhibition of mTORC235<\/a><\/sup>. It was therefore important to more fully assess the effects of IL-11 inhibition on liver function, metabolism and glucose utilization in old mice. As wild-type mice aged, there were increases in serum AST, ALT, cholesterol and triglycerides, which were collectively mitigated in old Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice (Fig. 2f<\/a> and Extended Data Fig. 5c, d<\/a>). Glucose tolerance test (GTT) and insulin tolerance test (ITT) profiles of old Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice were similar to those of young wild-type mice, whereas GTTs and ITTs of old wild-type mice showed impairment (Fig. 2g<\/a> and Extended Data Fig. 5e, f<\/a>). Indexed skeletal muscle mass was greater in both young and old Il11<\/em>\u2212\/\u2212<\/em><\/sup> mice compared with the equivalent wild-type mice (Extended Data Fig. 5g<\/a>).<\/p>\n","protected":false},"excerpt":{"rendered":"

To support the data generated in Il11ra1-deleted mice on a mixed C57BL6\/129 genetic background30 and to more deeply dissect age-related effects, we studied young (3-month-old) and aged (2-year-old) female mice with deletion of Il11 (Il11\u2212\/\u2212) on a C57BL6\/J background31. Immunoblots confirmed IL-11 up-regulation across tissues in old age in this additional strain (Fig. 1m). Old [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[412,418,269],"tags":[],"class_list":["post-197822","post","type-post","status-publish","format-standard","hentry","category-genetics","category-internet","category-life-extension"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/197822","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=197822"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/197822\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=197822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=197822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=197822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}