Positive correlation between mammalian life span and cellular resistance to stress

Positive correlation between mammalian life span and cellular resistance to stress
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DOI:
10.1016/s0891-5849(98)00323-2
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发表时间:
1999-03-01
影响因子:
7.4
通讯作者:
Kirkwood, TBL
Kirkwood, TBL
中科院分区:
医学1区
文献类型:
--
作者:
Kapahi, P;Boulton, ME;Kirkwood, TBL

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确定决定物种特定寿命的机制是理解衰老生物学的核心挑战。细胞压力会产生损伤,这些损伤可能会累积并导致衰老。进化理论预测,长寿的物种通过投资于更持久的躯体来确保它们的寿命,包括增强细胞对压力的抵抗力。为了研究长寿物种的细胞是否有更好的机制来应对氧化和非氧化应激,我们比较了8种不同寿命哺乳动物的原代皮肤成纤维细胞的细胞抗性。在百草枯、过氧化氢、过氧化叔丁基、亚砷酸钠和碱性pH(氢氧化钠)诱导下,用胸腺嘧啶掺入法测定细胞存活率。在所有应激条件下,细胞LD90与最大寿命呈显著正相关。用MTT法测定细胞存活率和比较不同物种的淋巴细胞时,也得到了类似的结果。细胞对各种氧化和非氧化应激的抵抗力与哺乳动物的寿命呈正相关。我们的研究结果支持这样一个概念,即调节细胞对压力反应的基因网络在衰老和长寿中具有重要的功能。(C) 1999 Elsevier Science Inc.;
Identifying the mechanisms determining species-specific life spans is a central challenge in understanding the biology of aging. Cellular stresses produce damage, that may accumulate and cause aging. Evolution theory predicts that long-lived species secure their longevity through investment in a more durable soma, including enhanced cellular resistance to stress. To investigate whether cells from long-lived species have better mechanisms to cope with oxidative and non-oxidative stress, we compared cellular resistance of primary skin fibroblasts from eight mammalian species with a range of life spans. Cell survival was measured by the thymidine incorporation assay following stresses induced by paraquat, hydrogen peroxide, tert-butyl hydroperoxide, sodium arsenite and alkaline pH (sodium hydroxide). Significant positive correlations between cell LD90 and maximum life span were found for all these stresses. Similar results were obtained when cell survival was measured by the MTT assay, and when lymphocytes from different species were compared. Cellular resistance to a variety of oxidative and non-oxidative stresses was positively correlated with mammalian longevity. Our results support the concept that the gene network regulating the cellular response to stress is functionally important in aging and longevity. (C) 1999 Elsevier Science Inc.