AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity.
AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity.
复制标题
DOI：
10.1111/j.1749-6632.2009.04019.x
复制
发表时间：
2009-07
影响因子：
5.2
通讯作者：
Brunet A
中科院分区：
文献类型：
--
作者：
Greer EL;Banko MR;Brunet A
衰老是通过单基因的修饰和环境的简单变化来调节的。连接胰岛素和FoxO转录因子的信号通路整合了环境刺激来调节寿命。FOXO转录因子通过蛋白激酶Akt响应胰岛素/生长因子信号被直接磷酸化，从而导致它们被隔离在细胞质中。在缺乏胰岛素/生长因子的情况下，FoxO因子转移到细胞核，在那里它们触发一系列细胞反应，包括对氧化应激的抵抗--这是一种与寿命延长高度相关的表型。我们最近的研究结果表明，FoxO转录因子也通过AMP激活的蛋白激酶(AMPK)途径对营养缺乏作出反应。能量敏感型AMPK在6个调节位点直接磷酸化FoxO转录因子。AMPK的磷酸化增强了FoxO的转录活性，导致了与逆境抗性相关的特定靶基因的表达和能量代谢的变化。AMPK-FoxO途径在饮食限制方案延长秀丽线虫寿命的能力中起着至关重要的作用。了解复杂的信号网络，将饮食限制等环境条件转化为基因表达的变化，从而延长寿命，对于找到延缓衰老和年龄相关性疾病发病的方法至关重要。
Aging is regulated by modifications in single genes and by simple changes in the environment. The signaling pathway connecting insulin to FoxO transcription factors integrates environmental stimuli to regulate lifespan. FoxO transcription factors are directly phosphorylated in response to insulin/growth factor signaling by the protein kinase Akt, thereby causing their sequestration in the cytoplasm. In the absence of insulin/growth factors, FoxO factors translocate to the nucleus where they trigger a range of cellular responses, including resistance to oxidative stress—a phenotype highly coupled with lifespan extension. Our recent results indicate that FoxO transcription factors are also regulated in response to nutrient deprivation by the AMP-activated protein kinase (AMPK) pathway. The energy-sensing AMPK directly phosphorylates FoxO transcription factors at six regulatory sites. AMPK phosphorylation enhances FoxO transcriptional activity, leading to the expression of specific target genes involved in stress resistance and changes in energy metabolism. The AMPK–FoxO pathway plays a crucial role in the ability of a dietary restriction regimen to extend lifespan in Caenorhabditis elegans. Understanding the intricate signaling networks that translate environmental conditions like dietary restriction into changes in gene expression that extend lifespan will be of critical importance to identify ways to delay the onset of aging and age-dependent diseases.
登录
查看更多内容
DOI：
10.1093/geronj/42.1.78
发表时间：
1987-01-01
期刊：
JOURNALS OF GERONTOLOGY
影响因子：
--
作者：
INGRAM, DK;WEINDRUCH, R;WALFORD, RL
通讯作者：
WALFORD, RL
影响因子：
3.5
作者：
Anisimova, VN;Ukraintseva, SV;Roth, GS
通讯作者：
Roth, GS
DOI：
10.1196/annals.1297.074
发表时间：
2004-01-01
期刊：
STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE: WHY GENUINE CONTROL OF AGING MAY BE FORESEEABLE
影响因子：
--
作者：
Ingram, DK;Anson, RM;Roth, GS
通讯作者：
Roth, GS
影响因子：
9.2
作者：
Kapahi, P;Zid, BM;Benzer, S
通讯作者：
Benzer, S
影响因子：
3.9
作者：
Anisimov, VN;Berstein, LM;Franceschi, C
通讯作者：
Franceschi, C