Department of Biology, University of Missouri-St. Louis, MO 63121-4499, USA.
Aging Cell. 2010 Apr;9(2):273-84. doi: 10.1111/j.1474-9726.2009.00542.x. Epub 2009 Dec 23.
Many laboratory models used in aging research are inappropriate for understanding senescence in mammals, including humans, because of fundamental differences in life history, maintenance in artificial environments, and selection for early aging and high reproductive rate. Comparative studies of senescence in birds and mammals reveal a broad range in rates of aging among a variety of taxa with similar physiology and patterns of development. These comparisons suggest that senescence is a shared property of all vertebrates with determinate growth, that the rate of senescence has been modified by evolution in response to the potential life span allowed by extrinsic mortality factors, and that most variation among species in the rate of senescence is independent of commonly ascribed causes of aging, such as oxidative damage. Individuals of potentially long-lived species, particularly birds, appear to maintain high condition to near the end of life. Because most individuals in natural populations of such species die of aging-related causes, these populations likely harbor little genetic variation for mechanisms that could extend life further, or these mechanisms are very costly. This, and the apparent evolutionary conservatism in the rate of increase in mortality with age, suggests that variation in the rate of senescence reflects fundamental changes in organism structure, likely associated with the rate of development, rather than physiological or biochemical processes influenced by a few genes. Understanding these evolved differences between long-lived and short-lived organisms would seem to be an essential foundation for designing therapeutic interventions with respect to human aging and longevity.
许多用于衰老研究的实验室模型都不适合理解哺乳动物(包括人类)的衰老,因为它们在生活史、人工环境中的维持以及对早期衰老和高繁殖率的选择方面存在根本差异。鸟类和哺乳动物衰老的比较研究揭示了具有相似生理学和发育模式的各种分类群中衰老率的广泛范围。这些比较表明,衰老性是所有具有定数生长的脊椎动物的共同特性,衰老的速度已经通过进化来适应由外在死亡因素允许的潜在寿命而改变,并且物种之间衰老率的大多数变化与通常归因于衰老的原因(如氧化损伤)无关。具有潜在长寿命的物种(特别是鸟类)的个体在接近生命结束时似乎仍能保持良好的状态。由于这些物种的自然种群中大多数个体死于与衰老相关的原因,这些种群可能很少具有可以进一步延长寿命的机制的遗传变异,或者这些机制非常昂贵。这一点以及与年龄相关的死亡率随年龄增加的明显进化保守性表明,衰老率的变化反映了生物体结构的根本变化,这可能与发育速度有关,而不是受少数基因影响的生理或生化过程。了解长寿和短寿生物体之间这些进化差异似乎是设计人类衰老和长寿治疗干预措施的重要基础。