The intrinsic aerobic capacity of an organism is thought to play a role in aging and longevity. Maximal respiratory rate capacity, a metabolic performance measure, is one of the best predictors of cardiovascular- and all-cause mortality. Rats selectively bred for high-(HCR) vs. low-(LCR) intrinsic running-endurance capacity have up to 31% longer lifespan. We found that positive changes in indices of mitochondrial health in cardiomyocytes (respiratory reserve, maximal respiratory capacity, resistance to mitochondrial permeability transition, autophagy/mitophagy, and higher lipids-over-glucose utilization) are uniformly associated with the extended longevity in HCR vs. LCR female rats. Cross-sectional heart metabolomics revealed pathways from lipid metabolism in the heart, which were significantly enriched by a select group of strain-dependent metabolites, consistent with enhanced lipids utilization by HCR cardiomyocytes. Heart–liver–serum metabolomics further revealed shunting of lipidic substrates between the liver and heart via serum during aging. Thus, mitochondrial health in cardiomyocytes is associated with extended longevity in rats with higher intrinsic exercise capacity and, probably, these findings can be translated to other populations as predictors of outcomes of health and survival.

生物体的内在有氧能力被认为在衰老和长寿中发挥作用。最大呼吸频率容量是一种代谢性能指标，是心血管和全因死亡率的最佳预测指标之一。针对高 (HCR) 与低 (LCR) 内在跑步耐力能力选择性繁殖的大鼠的寿命延长了 31%。我们发现心肌细胞线粒体健康指数的积极变化（呼吸储备、最大呼吸能力、对线粒体通透性转变的抵抗力、自噬/线粒体自噬和更高的脂质超过葡萄糖利用）与 HCR 与非正常人的寿命延长一致相关。 LCR 雌性大鼠。横断面心脏代谢组学揭示了心脏脂质代谢的途径，它们被一组选定的菌株依赖性代谢物显着富集，与 HCR 心肌细胞对脂质利用的增强一致。心肝血清代谢组学进一步揭示了衰老过程中通过血清在肝脏和心脏之间分流脂质底物。因此，心肌细胞中的线粒体健康与具有较高内在运动能力的大鼠的寿命延长有关，并且这些发现可能可以转化为其他人群作为健康和生存结果的预测指标。