Fibroblasts from long-lived bird species are resistant to multiple forms of stress
Fibroblasts from long-lived bird species are resistant to multiple forms of stress
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DOI：
10.1242/jeb.054643
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发表时间：
2011-06-01
影响因子：
2.8
通讯作者：
Miller, Richard A.
中科院分区：
文献类型：
--
作者：
Harper, James M.;Wang, Min;Miller, Richard A.
进化衰老理论认为，衰老是自然选择的力量随着实际年龄的增长而下降的结果。衰老生物学中比较研究的一个目标是确定遗传和生化机制，这些机制驱动衰老过程中的物种特异性差异，这些差异是生活史权衡的最终产物。我们假设，长寿鸟类的细胞比短命物种的细胞更能抵抗应激剂，而鸟类的细胞比类似大小的相对短命哺乳动物的细胞更能抵抗应激。我们测试了来自35种自由生活鸟类的原代成纤维细胞培养物对多种形式细胞应激的抵抗力，发现来自寿命较长物种的细胞系对镉引起的死亡具有抵抗力（R-2=0.27，P=0.002），百草枯（R-2=0.13，P=0.03），过氧化氢（R-2=0.09，P=0.07）和甲磺酸甲酯（R-2=0.13，P=0.03），以及在低葡萄糖培养基中观察到的代谢抑制（R-2=0.37，P < 0.01）。它们对紫外线辐射、毒胡萝卜素或衣霉素（未折叠蛋白反应的诱导剂）的抗性没有差异。这些结果在很大程度上是一致的，即使考虑到体重和生育能力的影响。来自长寿鸟类的细胞系也比来自短命鸟类的细胞增殖得更快，尽管增殖和应激抗性之间没有关系。最后，禽类成纤维细胞比啮齿类成纤维细胞对每种测试的应激源具有更大的抗性。这些结果支持了这样一种观点，即细胞对损伤的抵抗力可能是鸟类物种缓慢衰老和寿命长的进化的重要贡献者，并且可能有助于鸟类与相同体型的啮齿动物相比相对较长的寿命。
Evolutionary senescence theory postulates that aging results from the declining force of natural selection with increasing chronological age. A goal of comparative studies in the biology of aging is to identify genetic and biochemical mechanism(s) driving species-specific differences in the aging process that are the end product of life history trade-offs. We hypothesized that cells from long-lived bird species are more resistant to stress agents than are cells from short-lived species, and that cells from birds are more resistant to stress than are cells from relatively short-lived mammals of similar size. We tested primary fibroblast cultures from 35 species of free-living birds for their resistance to multiple forms of cellular stress and found that cell lines from longer-lived species were resistant to death caused by cadmium (R-2=0.27, P=0.002), paraquat (R-2=0.13, P=0.03), hydrogen peroxide (R-2=0.09, P=0.07) and methyl methanesulfonate (R-2=0.13, P=0.03), as well as to the metabolic inhibition seen in low-glucose medium (R-2=0.37, P < 0.01). They did not differ in their resistance to UV radiation, or to thapsigargin or tunicamycin, inducers of the unfolded protein response. These results were largely consistent even after accounting for the influence of body mass and phylogeny. Cell lines from longer-lived bird species also proliferate more rapidly than cells from short-lived birds, although there was no relationship between proliferation and stress resistance. Finally, avian fibroblasts were significantly more resistant than rodent fibroblasts to each of the tested stressors. These results support the idea that cellular resistance to injury may be an important contributor to the evolution of slow aging and long lifespan among bird species, and may contribute to the relatively long lifespan of birds compared with rodents of the same body size.