β‐Guanidinopropionic acid extends the lifespan of D rosophila melanogaster via an AMP ‐activated protein kinase‐dependent increase in autophagy
Authors: Si Yang
Jian-Guo Chen
Fang Wang
Di Li
Shan Jin
Jian-Kang Zhang
Li-Hong Long
Journal: Aging Cell (2015)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AMP-activated protein kinase; Drosophila; autophagy; autophagy-related protein 1; lifespan
Affiliations: Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China, College of Life Science Hubei University Wuhan 430062 China

Abstract:  Previous studies have demonstrated that AMP-activated protein kinase (AMPK) controls autophagy through the mammalian target of rapamycin (mTOR) and Unc-51 like kinase 1 (ULK1/Atg1) signaling, which augments the quality of cellular housekeeping, and that β-guanidinopropionic acid (β-GPA), a creatine analog, leads to a chronic activation of AMPK. However, the relationship between β-GPA and aging remains elusive. In this study, we hypothesized that feeding β-GPA to adult Drosophila produces the lifespan extension via activation of AMPK-dependent autophagy. It was found that dietary administration of β-GPA at a concentration higher than 900 mm induced a significant extension of the lifespan of Drosophila melanogaster in repeated experiments. Furthermore, we found that Atg8 protein, the homolog of microtubule-associated protein 1A/1B-light chain 3 (LC3) and a biomarker of autophagy in Drosophila, was significantly upregulated by β-GPA treatment, indicating that autophagic activity plays a role in the effect of β-GPA. On the other hand, when the expression of Atg5 protein, an essential protein for autophagy, was reduced by RNA interference (RNAi), the effect of β-GPA on lifespan extension was abolished. Moreover, we found that AMPK was also involved in this process. β-GPA treatment significantly elevated the expression of phospho-T172-AMPK levels, while inhibition of AMPK by either AMPK-RNAi or compound C significantly attenuated the expression of autophagy-related proteins and lifespan extension in Drosophila. Taken together, our results suggest that β-GPA can induce an extension of the lifespan of Drosophila via AMPK-Atg1-autophagy signaling pathway. 

Retracted: No

PubPeer comments:
 Fig 7E,  TUNEL staining showing the number of apoptotic cells in tumor sections. *[Below]* Fig 3D,  the proportion of apoptotic cells as determined by TUNEL from [Liu Yu (2018)] , a study of Amentoflavone from unrelated authors. ![file] , 
 Fig 5A: ![file] These FACS panels are like old friends by now. Compare with, e.g. 3B from [Liu Yu (2018)] : ![] [Dou et al. (2019)] ; [Xue et al (2019)] : ![] 2A from [Wang et al (2018)] . , 
 Here are galleries of histology slices from six papers, with six non-overlapping teams of nominal authors, sharing surprisingly many slices in common. Identication of each slice in terms of treatment and immunohistochemistry stain is arbitrary. Focussing on connections to the uppermost image, due to lack of colors. Clockwise from top: Fig 7F from [Pan et al (2018)] . Physcion and hepatoceulllar carcinoma. 7E from [Niu et al (2019)] . Physcion 8-O-u03b2-glucopyranoside and gastric cancer. Fig 6D from [Wang et al (2018)] . Physcion 8-O-u03b2-glucopyranoside and clear-cell renal cell carcinoma. 6C from [Zou et al (2018)] . Euxanthone and epithelial ovarian cancer. 8C from [Liu et al (2018)] . Hispidulin and colorectal cancer. 8D from [Dou et al (2019)] . Physcion 8-O-u03b2-Glucopyranoside and Testicular Germ Cell Tumors. ![] , 
 Fig 7E, here at upper right. Also appears as 6(b) of [Han et al (2019)] , upper left. ![file] , 
 *[Below]* Fig 6F. *[Above]* Fig 6B from [He et al (2020)] .  AIF suppresses the tumor growth of GBM in vivo. .... B. The relative levels of ki-67, p27, cyclin D1, CDK4 and CDK6 in tumor tissues were examined by using IHC. ![file] (I only just noticed the double appearance of the panel marked with the red box). , 
 Above:  Fig. 6. Physcion induces autophagy in the HCC cells by inactivating the JAK2 STAT3 pathway. ... (F) Cell migration and invasion abilities assayed by wound healing and Transwell invasion protocols. Middle: Fig 2B from [Gao et al (2017)] :  Effects of hispidulin on cell metastatic ability. ... B: Transwell invasion assay analyzed cell invasion in Caki-2 and A498 cells after treatment with hispidulin (10 u00b5M or 20 u00b5M). Bottom: Figs 2E ( MiR-137 restrains cell invasion ) and 3E ( Anti-miR-137 stimulates cell invasion ) from [Wang et al (20198)] . ![file] Duplicated panels marked. , 
 [Retraction Note dated 1 August 2020] :  This article has been retracted at the request of the Editor-in-Chief and the authors, as panels from Fig. 6F appear as similar to panels from Fig. 2B of the article published by Ming-Quan Gao, Hui Gao, Mei Han, Kai-Li Liu, Jian-Jun Peng and Yan-Tao Han in the American Journal of Cancer Research 7 (2017) 1501u20131514 https: www.ncbi.nlm.nih.gov pmc articles PMC5523031 and Figs. 2E and 3E of the article published by Meizhi Wang, Hui Gao, Haijun Qu, Jing Li, Kaili Liu and Zhiwu Han in Pharmacological Reports 70 (2018) 963u2013971 https: doi.org 10.1016 j.pharep.2018.04.006.  Also, the Vehicle panel from Fig. 7E appears as similar to the Vehicle panel from Fig. 3D of the article published by Bo Liu and Shuo Yu in Biomedicine Pharmacotherapy 107 (2018) 243u2013253 https: doi.org 10.1016 j.biopha.2018.07.177.  Fig. 7E appears also as similar to Fig. 6(b) of the article published by Mei Han, Hui Gao, Jing Xie, Yin-ping Yuan, Quan Yuan, Ming-quan Gao, Kai-li Liu, Xue-hong Chen, Yan-tao Han and Zhi-wu Han in Acta Pharmacologica Sinica volume 40 (2019) 666u2013676 https: doi.org 10.1038 s41401-018-0159-7.  Moreover, panels from Fig. 7F appear as similar to panels from Fig. 7E of the Reference [1], Fig. 6D of the Reference [2], Fig. 6C of the Reference [3], Fig. 8C of the Reference [4], Fig. 8D of the Reference [5] and Fig. 6B of the Reference [6].  One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. ,