Long-term IGF-I exposure decreases autophagy and cell viability.
Long-term IGF-I exposure decreases autophagy and cell viability.
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DOI：
10.1371/journal.pone.0012592
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发表时间：
2010-09-07
期刊：
影响因子：
3.7
通讯作者：
Sell C
中科院分区：
文献类型：
--
作者：
Bitto A;Lerner C;Torres C;Roell M;Malaguti M;Perez V;Lorenzini A;Hrelia S;Ikeno Y;Matzko ME;McCarter R;Sell C
尽管igf - 1是许多细胞类型的营养因子，并且在急性环境中对多种形式的损伤具有保护作用，但已发现igf - 1信号的减少可以延长多种生物体的寿命。IGF-I信号减少所带来的寿命延长表明，IGF-I信号的急性和慢性影响可能存在差异。我们利用静止的人成纤维细胞研究了igf - 1长期刺激可能在细胞水平上产生负面影响的可能性。我们发现，通过集落形成试验判断，暴露于igf - 1 14天的成纤维细胞的长期生存能力降低，并伴有衰老细胞的积累。此外，我们观察到在长期igf - 1处理的培养中，线粒体去极化细胞的积累和自噬的减少。对IGF-I水平降低的小鼠进行的检查显示，自噬增强，来自这些小鼠的成纤维细胞相对于对照组具有更大的线粒体质量，这表明在IGF-I水平降低的动物中发生了线粒体转换的变化。结果表明，慢性igf - 1刺激导致线粒体功能障碍和细胞活力降低。
A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.
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影响因子：
15.9
作者：
Lembo, G;Rockman, HA;PowellBraxton, L
通讯作者：
PowellBraxton, L
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
3.5
作者：
Gu, YP;Wang, CJ;Cohen, A
通讯作者：
Cohen, A
影响因子：
11.4
作者：
Cuervo, Ana Maria
通讯作者：
Cuervo, Ana Maria
DOI：
10.1073/pnas.111158898
发表时间：
2001-06-05
影响因子：
11.1
作者：
Flurkey, K;Papaconstantinou, J;Harrison, DE
通讯作者：
Harrison, DE