The mechanisms underlying metabolic decline during ageing are not well understood. A new study in Cell Metabolism identifies IgG antibodies as factors that accumulate in white adipose tissue (WAT) during ageing, driving tissue fibrosis and impaired metabolic health in mice.

“Leveraging our understanding of ageing research, we naturally sought to investigate whether interventions targeting ageing could influence IgG accumulation in adipose tissue,” says corresponding author Liheng Wang. Considering previous work showing the anti-ageing effects of caloric restriction, they investigated IgG accumulation in calorie-restricted mice (CR-mice). Interestingly, age-linked IgG accumulation was decreased in CR-mice and administering IgG to CR-mice counteracted the beneficial effects of caloric restriction on glucose metabolism. Delving into the mechanisms, the researchers found that IgG was activating adipose tissue-resident macrophages. The activated macrophages induced fibrosis in WAT, which is detrimental for systemic metabolic health.

衰老过程中代谢下降的机制尚不清楚。《细胞代谢》中的一项新研究发现 IgG 抗体是衰老过程中在白色脂肪组织 (WAT) 中积累的因子，可导致小鼠组织纤维化并损害代谢健康。

“利用我们对衰老研究的理解，我们自然地试图研究针对衰老的干预措施是否会影响脂肪组织中的 IgG 积累，”通讯作者 Liheng Wang 说。考虑到之前的研究表明热量限制具有抗衰老作用，他们研究了热量限制小鼠（CR-小鼠）中 IgG 的积累。有趣的是，CR 小鼠中与年龄相关的 IgG 积累减少，并且给 CR 小鼠施用 IgG 抵消了热量限制对葡萄糖代谢的有益影响。通过深入研究其机制，研究人员发现 IgG 正在激活脂肪组织中的巨噬细胞。活化的巨噬细胞诱导 WAT 纤维化，这对全身代谢健康有害。