Nugent William H, Golub Aleksander S, Pittman Roland N, Song Bjorn K
Song Biotechnologies LLC., Baltimore, MD, 21030, USA.
Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Biogerontology. 2025 Jan 8;26(1):38. doi: 10.1007/s10522-024-10180-0.
Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms critical to the loss of skeletal muscle function in aging. Here we present baseline physiological data of 61 male, Sprague Dawley rats at 3, 6, 12, 18, and 24 months of age. Anesthetized animals were surgically prepared for femoral arterial and venous cannulations, tracheal intubation, and exteriorization of the spinotrapezius muscle. Measurements included cardiovascular function, blood gases, and peripheral tissue interstitial oxygen tension (PO) using phosphorescence quenching microscopy. Intrinsic heart rates decreased with age without significant changes to blood pressure. Arterial oxygen tension declined 17% by 18 and 24 Months (p < 0.05) while pCO and PO were unchanged. Lactate was elevated at 12 and 18 Months along with an alkaline shift in blood pH. Heart rate and decreased pO decoupled from pCO are conserved phenomena in human aging. The continuity of resting PO despite an anaerobic shift in metabolism may be due to declining mitochondrial function and dysregulation of the vascular response to hypoxemia, which are also present in aged humans. These physiological and microcirculatory data offer a useful experimental model for investigating the detailed changes in oxygen supply and demand that affect senescing skeletal muscles in rats and humans.
人类正经历着前所未有的增长和寿命延长，然而对于衰老的特征、机制和病理状况仍存在知识空白。纵向研究中进行侵入性测量和长期控制条件是不可行的，因此需要替代动物模型。大鼠寿命较短（2 - 3年），其心血管系统具有可转化性，而Sprague Dawley大鼠的微循环制剂是研究对衰老过程中骨骼肌功能丧失至关重要的氧运输机制的关键。在此，我们展示了61只3、6、12、18和24月龄雄性Sprague Dawley大鼠的基线生理数据。对麻醉的动物进行手术准备，用于股动脉和静脉插管、气管插管以及斜方肌的外置。测量包括心血管功能、血气以及使用磷光猝灭显微镜测量外周组织间质氧张力（PO）。固有心率随年龄下降，血压无显著变化。到18个月和24个月时，动脉氧张力下降了17%（p < 0.05），而pCO和PO不变。乳酸在12个月和18个月时升高，同时血液pH值出现碱化偏移。心率下降和pO与pCO解耦是人类衰老中的保守现象。尽管代谢发生厌氧转变，但静息PO的连续性可能是由于线粒体功能下降以及对低氧血症的血管反应失调，这些在老年人类中也存在。这些生理和微循环数据为研究影响大鼠和人类衰老骨骼肌的氧供需详细变化提供了一个有用的实验模型。
