Department of Medicine, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Department of Cell Biology and Molecular Medicine, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Aging Cell. 2023 Apr;22(4):e13791. doi: 10.1111/acel.13791. Epub 2023 Mar 10.
Enhanced exercise capacity is not only a feature of healthful aging, but also a therapy for aging patients and patients with cardiovascular disease. Disruption of the Regulator of G Protein Signaling 14 (RGS14) in mice extends healthful lifespan, mediated by increased brown adipose tissue (BAT). Accordingly, we determined whether RGS14 knockout (KO) mice exhibit enhanced exercise capacity and the role of BAT in mediating exercise capacity. Exercise was performed on a treadmill and exercise capacity was assessed by maximal running distance and work to exhaustion. Exercise capacity was measured in RGS14 KO mice and their wild types (WT), and also in WT mice with BAT transplantation from RGS14 KO mice or from other WT mice. RGS14 KO mice demonstrated 160 ± 9% increased maximal running distance and 154 ± 6% increased work to exhaustion, compared to WT mice. RGS14 KO BAT transplantation to WT mice, resulted in a reversal of phenotype, with the WT mice receiving the BAT transplant from RGS14 KO mice demonstrating 151 ± 5% increased maximal running distance and 158 ± 7% increased work to exhaustion, at three days after BAT transplantation, compared to RGS14 KO donors. BAT transplantation from WT to WT mice also resulted in increased exercise performance, but not at 3 days, but only at 8 weeks after transplantation. The BAT induced enhanced exercise capacity was mediated by (1) mitochondrial biogenesis and SIRT3; (2) antioxidant defense and the MEK/ERK pathway, and increased hindlimb perfusion. Thus, BAT mediates enhanced exercise capacity, a mechanism more powerful with RGS14 disruption.
增强的运动能力不仅是健康衰老的特征，也是衰老患者和心血管疾病患者的治疗方法。在小鼠中，G 蛋白信号转导调节因子 14（RGS14）的破坏通过增加棕色脂肪组织（BAT）延长健康寿命。因此，我们确定 RGS14 敲除（KO）小鼠是否表现出增强的运动能力，以及 BAT 在介导运动能力中的作用。在跑步机上进行运动，通过最大跑步距离和疲劳工作来评估运动能力。在 RGS14 KO 小鼠及其野生型（WT）以及从 RGS14 KO 小鼠或其他 WT 小鼠移植 BAT 的 WT 小鼠中测量运动能力。与 WT 小鼠相比，RGS14 KO 小鼠的最大跑步距离增加了 160±9%，疲劳工作增加了 154±6%。将 RGS14 KO BAT 移植到 WT 小鼠中，导致表型逆转，接受来自 RGS14 KO 小鼠的 BAT 移植的 WT 小鼠的最大跑步距离增加了 151±5%，疲劳工作增加了 158±7%，在 BAT 移植后 3 天与 RGS14 KO 供体相比。WT 向 WT 小鼠的 BAT 移植也导致运动表现增加，但不是在 3 天时，而是仅在移植后 8 周时。BAT 诱导的增强的运动能力是通过（1）线粒体生物发生和 SIRT3；（2）抗氧化防御和 MEK/ERK 途径以及增加后肢灌注来介导的。因此，BAT 介导增强的运动能力，这种机制在 RGS14 破坏时更为强大。
