A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice.
A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice.
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Glb1-2A-mCherry 报告基因监测中年小鼠的全身衰老并预测寿命
DOI：
10.1038/s41467-022-34801-9
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发表时间：
2022-11-17
影响因子：
16.6
通讯作者：
Liu, Baohua
中科院分区：
文献类型：
--
作者：
Sun, Jie;Wang, Ming;Zhong, Yaqi;Ma, Xuan;Sun, Shimin;Xu, Chenzhong;Peng, Linyuan;Li, Guo;Zhang, Liting;Liu, Zuojun;Ai, Ding;Liu, Baohua
生理功能的逐渐衰退和年龄相关疾病风险的增加对健康老龄化提出了挑战。多种抗衰老操作，如senolytics，已被证明对健康有益;然而，缺乏在全身水平标记体内衰老的生物标志物，从而阻碍了抗衰老应用。在这项研究中，我们在Glb 1基因位点产生了Glb 1 +/m-Glb 1 -2A-mCherry（GAC）报告基因等位基因，该基因编码溶酶体β-半乳糖苷酶--一种在老年小鼠组织中升高的酶。在一组中年（9至13个月）Glb 1 +/m小鼠中建立了GAC信号与实足年龄之间的线性相关性。高GAC信号与心脏肥大和寿命缩短密切相关。此外，GAC信号在肺中由博来霉素诱导的病理性衰老中呈指数增加。衰老清除剂达沙替尼和槲皮素（D + Q）降低博来霉素处理的小鼠中的GAC信号。因此，Glb 1 -2A-mCherry报告基因小鼠监测系统性衰老和功能衰退，预测寿命，并可能促进对衰老机制的理解，并有助于开发抗衰老干预措施。监测体内老化过程具有挑战性。在这里，作者生成了Glb 1 +/mGlb 1 -2A-mCherry（GAC）报告小鼠模型，其中GAC信号始终与细胞衰老，心脏肥大和寿命缩短的既定生物标志物相关，这可能有助于开发抗衰老干预措施的研究。
The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1+/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions. Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
64.5
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
通讯作者：
Sharpless NE
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
影响因子：
20.1
作者：
North BJ;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS