Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice.
Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice.
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DOI：
10.18632/aging.101446
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发表时间：
2018-05-20
期刊：
影响因子：
--
通讯作者：
Selman C
中科院分区：
文献类型：
--
作者：
Page MM;Schuster EF;Mudaliar M;Herzyk P;Withers DJ;Selman C
饮食限制（DR）是研究最广泛的非遗传干预，能够延长多个分类群的寿命。基因的调节，主要是在胰岛素/胰岛素样生长因子信号传导（IIS）和雷帕霉素（mTOR）信号传导途径的机制靶也起到延长模型生物体寿命的作用。例如，缺乏胰岛素受体底物-1（IRS 1）的小鼠寿命较长，并可防止几种与年龄相关的病理。然而，目前尚不清楚这些特定的干预措施如何机械地产生其有益的影响。在这里，我们研究了野生型和IRS 1基因敲除小鼠的转录反应，这些小鼠随意喂食（WTAL和KOAL）或喂食30%DR饮食（WTDR或KODR）。使用RNAseq方法，我们注意到差异表达基因的高相关系数存在于WTDR和KOAL小鼠的相同组织中，并且这些小鼠之间共享许多代谢特征。总体而言，我们报告说，在组织特异性转录反应之间存在显着的重叠长寿DR小鼠和IRS 1空小鼠。然而，有证据表明KOAL和KODR之间的转录签名和某些表型测量之间存在脱节，因为观察到对体重的累加效应，但在转录水平上，DR在这些已经长寿的小鼠中诱导了一组独特的基因。
Dietary restriction (DR) is the most widely studied non-genetic intervention capable of extending lifespan across multiple taxa. Modulation of genes, primarily within the insulin/insulin-like growth factor signalling (IIS) and the mechanistic target of rapamycin (mTOR) signalling pathways also act to extend lifespan in model organisms. For example, mice lacking insulin receptor substrate-1 (IRS1) are long-lived and protected against several age-associated pathologies. However, it remains unclear how these particular interventions act mechanistically to produce their beneficial effects. Here, we investigated transcriptional responses in wild-type and IRS1 null mice fed an ad libitum diet (WTAL and KOAL) or fed a 30% DR diet (WTDR or KODR). Using an RNAseq approach we noted a high correlation coefficient of differentially expressed genes existed within the same tissue across WTDR and KOAL mice and many metabolic features were shared between these mice. Overall, we report that significant overlap exists in the tissue-specific transcriptional response between long-lived DR mice and IRS1 null mice. However, there was evidence of disconnect between transcriptional signatures and certain phenotypic measures between KOAL and KODR, in that additive effects on body mass were observed but at the transcriptional level DR induced a unique set of genes in these already long-lived mice.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
生长激素受体的破坏可防止卡路里的限制改善胰岛素作用和寿命。
影响因子：
3.7
作者：
Bonkowski MS;Dominici FP;Arum O;Rocha JS;Al Regaiey KA;Westbrook R;Spong A;Panici J;Masternak MM;Kopchick JJ;Bartke A
通讯作者：
Bartke A
影响因子：
4.6
作者：
Essers P;Tain LS;Nespital T;Goncalves J;Froehlich J;Partridge L
通讯作者：
Partridge L
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L