Economos A C, Miquel J, Ballard R C, Blunden M, Lindseth K A, Fleming J, Philpott D E, Oyama J
Arch Gerontol Geriatr. 1982 Dec;1(4):349-63. doi: 10.1016/0167-4943(82)90035-8.
Ever since Pearl proposed the rate of living theory of aging numerous studies have demonstrated its validity in poikilotherms. In mammals, however, satisfactory experimental demonstration is still lacking because an externally imposed increase of basal metabolic rate of these animals (e.g. by placement in the cold) is usually accompanied by general homeostatic disturbance and stress. The present study was based on the finding that rats exposed to slightly increased gravity are able to adapt with little chronic stress but at a higher level of basal metabolic expenditure (increased 'rate of living'). The rate of aging of 17-mth-old rats that had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 mth was larger than of controls as shown by apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration (reduced 'efficiency': 20% larger ADP: 0 ratio, P less than 0.01; reduced 'speed': 8% lower respiratory control ratio, P less than 0.05). On the other hand, steady-state food intake per day per kg body weight, which is presumably proportional to 'rate of living' or specific basal metabolic expenditure, was about 18% higher than in controls (P less than 0.01) after an initial 2-mth adaptation period. Finally, though half of the centrifuged animals lived only a little shorter than controls (average about 343 vs. 364 days on the centrifuge, difference statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for controls, computed from onset of centrifugation, or 11% shorter (P less than 0.01). Therefore, these results show that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.
自从珀尔提出衰老的生活率理论以来，众多研究已在变温动物中证明了其有效性。然而，在哺乳动物中，仍缺乏令人满意的实验证明，因为这些动物基础代谢率的外部增加（例如置于寒冷环境中）通常伴随着整体稳态紊乱和应激。本研究基于这样一个发现：暴露于轻度增加的重力环境下的大鼠能够在几乎没有慢性应激的情况下适应，但基础代谢消耗水平更高（“生活率”增加）。在动物离心机中暴露于3.14倍正常重力8个月的17月龄大鼠的衰老速度比对照组更快，这表现为心脏和肾脏中脂褐素含量明显升高、心脏组织线粒体数量减少且体积增大、肝脏线粒体呼吸功能较差（“效率”降低：ADP:O比值高20%，P<0.01；“速度”降低：呼吸控制率低8%，P<0.05）。另一方面，在最初2个月的适应期后，每千克体重每天的稳态食物摄入量，大概与“生活率”或特定基础代谢消耗成正比，比对照组高约18%（P<0.01）。最后，虽然一半的离心处理动物的存活时间仅比对照组略短（离心机上平均约343天对364天，差异无统计学意义），但从离心开始计算，其余一半（最长存活者）在离心机上平均存活520天（范围483 - 572天），而对照组平均存活574天（范围502 - 615天），即短11%（P<0.01）。因此，这些结果表明，与正常重力下的对照组相比，适应超重的年轻成年大鼠基础代谢水平适度增加，伴随着器官衰老速度大致相似的增加和存活率降低，这与珀尔的衰老生活率理论一致，该理论此前仅在变温动物中得到实验证明。
