Data for Early-onset dietary restriction maintains mitochondrial health, autophagy and ER function in the left ventricle during aging

Dietary restriction (DR) exerts healthy benefits, including heart functions. However, the cardioprotective role of DR is till controversial among researchers due to the variation of DR conditions. The present study focuses on the protective effect of early-onset DR on cardiac injury using mitochondrial structure and expression of protein associated with mitochondrial homeostasis, autophagy and endoplasmic reticulum (ER) function as measures. Methods: Two-month-old mice were fed with a breeding diet ad libitum (AL) or DR (60% of AL) for 3 (Young) or 20 (Aged) months. Results: Body weight increased with aging, whereas DR treatment kept body weight consistent. DR mice exhibited a higher relative heart weight than AL mice. DR mice displayed lower plasma glucose levels, compared with AL groups. Furthermore, Aged-AL, but not Aged-DR mice, had increased collagen content and morphological distortions in the left ventricle (LV). Aged-DR mice had a higher ATP and lower TBARS in the LV than Aged-AL mice. Mitochondrial morphology was detected by electron microscopy; Aged-AL mice had increased abnormal morphology of mitochondria. Treatment with DR reduced abnormal mitochondrial accumulation. Aging elevated the protein expressions of mitochondrial functions and ER-induced apoptosis. Aging downregulated autophagy-related proteins and chaperones in the heart. Dietary restriction reversed those protein expressions. Conclusions: The present study demonstrated a beneficial effect of early onset DR on cardiac aging. The age-dependent mitochondrial dysfunction and protein quality control dysregulation was significantly reversed by long-term DR, demonstrating a concordance with the beneficial effect in the heart.

饮食限制（Dietary Restriction, DR）可发挥多种健康益处，包括对心脏功能的保护作用。然而，由于饮食限制的干预条件存在差异，其心脏保护作用在研究者中仍存在争议。本研究以线粒体结构、线粒体稳态相关蛋白表达、自噬及内质网（Endoplasmic Reticulum, ER）功能作为检测指标，探究早期启动饮食限制对心脏损伤的保护作用。
方法：选取2月龄小鼠，分别给予自由采食（Ad Libitum, AL）繁育饲料或饮食限制饲料（饲喂量为自由采食组的60%），分别饲养3个月（青年组）或20个月（老年组）。
结果：随着月龄增长，自由采食组小鼠体重逐渐升高，而饮食限制组小鼠体重维持稳定。饮食限制组小鼠的心脏相对重量高于自由采食组小鼠。与自由采食组相比，饮食限制组小鼠的血浆葡萄糖水平更低。此外，老年自由采食组小鼠的左心室（Left Ventricle, LV）胶原含量升高且形态出现畸变，而老年饮食限制组小鼠未出现此类现象。与老年自由采食组小鼠相比，老年饮食限制组小鼠左心室中的三磷酸腺苷（Adenosine Triphosphate, ATP）水平更高，而硫代巴比妥酸反应物（Thiobarbituric Acid Reactive Substances, TBARS）水平更低。通过电子显微镜检测线粒体形态：老年自由采食组小鼠的线粒体形态异常比例升高，而饮食限制干预可减少异常线粒体的累积。衰老会提升心脏组织中线粒体功能相关蛋白及内质网诱导凋亡相关蛋白的表达水平；衰老会下调心脏组织中自噬相关蛋白及分子伴侣的表达水平。饮食限制可逆转上述蛋白表达的异常变化。
结论：本研究证实了早期启动饮食限制对心脏衰老的保护作用。长期饮食限制可显著逆转衰老诱导的线粒体功能障碍与蛋白质质量控制失调，这与饮食限制在心脏中的有益作用相一致。