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Yao Dang Yongpan An Jinzhao He Boyue Huang Jie Zhu Miaomiao Gao Shun Zhang Xin Wang Baoxue Yang Zhengwei Xie 《Aging cell》2020,19(1)
Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti‐aging. This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts (2BS and WI38). BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence‐associated β‐galactosidase (SA‐β‐gal)‐positive cell rates of late PD cells grown in the BBR‐containing medium were ~72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically, BBR improved cell growth and proliferation by promoting entry of cell cycles from the G0 or G1 phase to S/G2‐M phase. Most importantly, BBR extended the lifespan of chemotherapy‐treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti‐aging medicine. 相似文献
164.
Oyundari Amartuvshin Chi‐Hung Lin Shao‐Chun Hsu Shih‐Han Kao Alvin Chen Wei‐Chun Tang Han‐Lin Chou Dong‐Lin Chang Yen‐Yang Hsu Bai‐Shiou Hsiao Elham Rastegari Kun‐Yang Lin Yu‐Ting Wang Chi‐Kuang Yao Guang‐Chao Chen Bi‐Chang Chen Hwei‐Jan Hsu 《Aging cell》2020,19(8)
Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration. 相似文献
165.
Hui Yao Liqun Wang Jia Guo Weimin Liu Jingjing Li Yingxiao Wang Linhong Deng Mingxing Ouyang 《Molecular & cellular biomechanics : MCB》2020,17(3):101-111
Prostate cancer is the most common cancer among men beyond 50 years
old, and ranked the second in mortality. The level of Prostate-specific antigen
(PSA) in serum has been a routine biomarker for clinical assessment of the cancer
development, which is detected mostly by antibody-based immunoassays. The
proteolytic activity of PSA also has important functions. Here a genetically
encoded biosensor based on fluorescence resonance energy transfer (FRET) technology was developed to measure PSA activity. In vitro assay showed that the
biosensor containing a substrate peptide ‘RLSSYYSGAG’ had 400% FRET
change in response to 1 µg/ml PSA within 90 min, and could detect PSA activity
at 25 ng/ml. PSA didn’t show enzymatic activity toward the biosensor in serum
solution, likely reflecting the existence of other inhibitory factors besides Zn2+.
By expressing the biosensor on cell plasma membrane, the FRET responses were
significant, but couldn’t distinguish well the cultured prostate cancer cells from
non-prostate cancer cells under microscopy imaging, indicating insufficient speci-
ficity to PSA. The biosensor with the previously known ‘HSSKLQ’ substrate
showed little response to PSA in solution. In summary, we developed a genetically encoded FRET biosensor to detect PSA activity, which may serve as a useful
tool for relevant applications, such as screening PSA activation substrates or inhibitors; the purified biosensor protein can also be an alternative choice for measuring PSA activity besides currently commercialized Mu-HSSKLQ-AMC substrate
from chemical synthesis. 相似文献
166.
Jiaxin Zheng Shoulin Zhang Huijun Chen Xiaojun Cai Chunjian Zhang Shuhua Li Yabin Zhou Jing Shang Shunyu Liang Fengzhen Yao 《Cell biology international》2020,44(1):189-199
Protosappanin‐A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b‐9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real‐time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b‐9‐induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p‐AKT/p‐mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K‐AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p‐AKT/p‐mTOR levels induced by IGF‐1 (a PI3K‐AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT‐mTOR signaling. 相似文献
167.
Jianping Duan Ying Li Jie Du Erzhen Duan Yuyu Lei Shimei Liang Xian Zhang Xin Zhao Yunchao Kan Lunguang Yao Xinfeng Yang Xingtan Zhang Xiangwei Wu 《Molecular ecology resources》2020,20(5):1372-1383
Antheraea pernyi is a semi‐domesticated lepidopteran insect species valuable to the silk industry, human health, and ecological tourism. Owing to its economic influence and developmental properties, it serves as an ideal model for investigating divergence of the Bombycoidea super family. However, studies on the karyotype evolution and functional genomics of A. pernyi are limited by scarce genomic resource. Here, we applied PacBio sequencing and chromosome structure capture technique to assemble the first high‐quality A. pernyi genome from a single male individual. The genome is 720.67 Mb long with 49 chromosomes and a 13.77‐Mb scaffold N50. Approximately 441.75 Mb, accounting for 60.74% of the genome, was identified as repeats. The genome comprises 21,431 protein‐coding genes, 85.22% of which were functionally annotated. Comparative genomics analysis suggested that A. pernyi diverged from its common ancestor with A. yamamai ~30.3 million years ago, and that chromosome fission contributed to the increased chromosome number. The genome assembled in this work will not only facilitate future research on A. pernyi and related species but also help to progress comparative genomics analyses in Lepidoptera. 相似文献
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