1.中山大学附属第一医院老年医学科,广东 广州 510080
2.中山大学附属第一医院神经内科,广东 广州 510080
况琪斐,在读硕士生,研究方向:衰老与认知,E-mail:Kuangqf@mail2.sysu.edu.cn
纸质出版日期:2021-03-20,
收稿日期:2021-01-06,
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况琪斐,陈巧超,张玲等.阿魏酸通过胰岛素/IGF信号通路和DAF-16促进秀丽隐杆线虫寿命和应激抵抗力[J].中山大学学报(医学科学版),2021,42(02):193-201.
KUANG Qi-fei,CHEN Qiao-chao,ZHANG Ling,et al.Ferulic Acid Promotes Longevity and Stress Tolerance via the Insulin/IGF Signaling Pathway and DAF-16 in Caenorhabditis Elegans[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(02):193-201.
况琪斐,陈巧超,张玲等.阿魏酸通过胰岛素/IGF信号通路和DAF-16促进秀丽隐杆线虫寿命和应激抵抗力[J].中山大学学报(医学科学版),2021,42(02):193-201. DOI:
KUANG Qi-fei,CHEN Qiao-chao,ZHANG Ling,et al.Ferulic Acid Promotes Longevity and Stress Tolerance via the Insulin/IGF Signaling Pathway and DAF-16 in Caenorhabditis Elegans[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(02):193-201. DOI:
目的
2
观察阿魏酸对秀丽隐杆线虫寿命及应激抵抗能力的影响,探究其可能机制。
方法
2
使用秀丽隐杆线虫作为抗衰老模型,给予不同浓度的阿魏酸(0、1、10、50 mmol/L),探究其对线虫寿命、抗应激能力、脂褐素水平的调控作用;使用qPCR筛选衰老相关基因,采用
daf-2
(
DR1572
)、
daf-16
(
CF1038
)突变体线虫,对阿魏酸的潜在作用机理进行初步探讨。
结果
2
与空白对照组相比,阿魏酸能明显延长秀丽隐杆线虫寿命并提高抗氧化应激和热应激能力(
P
<0.001),抑制与衰老相关的脂褐素的沉积(
P
<0.001),同时不影响生育力和发育(
P
>0.05)。用50 mmol/L阿魏酸组喂养线虫后,
daf-2
、
akt-2
和
age-1
基因的mRNA表达水平下调(
P
<0.05),
daf-16
基因的mRNA表达水平上调(
P
<0.05),并上调其下游靶基因
sod-3
、
clk-2
的mRNA表达,以及下调
ctl-1
、
dod-17
的mRNA表达(
P
<0.05)。50 mmol/L阿魏酸处理后DAF-16::GFP在细胞核定位的线虫比例从(5.3±1.5)%增加到(28±3)%。
daf-2
(
DR1572
)、
daf-16
(
CF1038
)突变体线虫在50 mmol/L阿魏酸处理后,寿命未见明显延长(
P
>0.05)。
结论
2
阿魏酸可通过胰岛素/IGF信号通路,促进 DAF-16 的核定位,提高机体应激抵抗能力,并延长线虫寿命。
Objective
2
To investigate the effect on life extension and the mechanism of ferulic acid in
Caenorhabditis elegans.
Methods
2
We used
C. elegans
as an anti-aging model, and different concentrations of ferulic acid (0, 1, 10, 50 mmol/L) were given to explore its regulatory effects on the lifespan, anti-stress ability, and lipofuscin level of
C. elegans
. And we used qPCR to screen senescence related genes, and
DAF-2
(
DR1572
) and
DAF-16
(
CF1038
) mutants were used to investigate the potential mechanism of ferulic acid.
Results
2
Compared with the blank control group, ferulic acid significantly extended the lifespan of
C. elegans
and increased its antioxidant and thermal stress (
P
<0.001), inhibited the accumulation of lipofuscin related to aging (
P
<
0.001), and did not affect its fertility and body shape (
P
>0.05) . After feeding nematode in the 50 mmol/L ferulic acid group, mRNA expression levels of
DAF-2
,
Akt-2
and
AGE-1
genes were down-regulated (
P
<
0.05), mRNA expression levels of
DAF-16
genes were up-regulated (
P
<0.05) and the expression levels of its downstream target genes
sod-3
,
ctl-1
,
clk-2
and
dod-17
were activated (
P
<0.05). After 50 mmol/L ferulic acid treatment, the proportion of daf-16 ::GFP in the nematode cell nucleus increased from (5.3±1.5) % to (28±3) %. The lifespan of
DAF-2
(
DR1572
) and
DAF-16
(
CF1038
)
mutant nematodes was not significantly extended after treatment with 50 mmol/L ferulic acid (
P
>0.05).
Conclusions
2
Ferulic acid can promote the nuclear localization of
daf-16
through insulin /IGF signaling pathway, improve the stress resisting ability of the organism, and prolong the lifespan of nematode.
阿魏酸胰岛素/IGF信号通路DAF-16衰老秀丽隐杆线虫
ferulic acidinsulin/IGF signaling pathwayDAF-16agingC. elegans
Olovnikov AM. Aging theories[M]. Cham:Springer International Publishing, 2019: 1-9.
López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153(6): 1194-1217.
Stroustrup N. Measuring and modeling interventions in aging[J]. Curr Opin Cell Biol, 2018, 55: 129-138.
Shen P, Yue Y, Park Y. A living model for obesity and aging research: Caenorhabditis elegans[J]. Crit Rev Food Sci Nutr, 2018, 58(5): 741-754.
Gems D, Riddle DL. Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans[J]. Genetics, 2000, 154(4): 1597-1610.
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing[J]. Nature, 2000, 408(6809): 239-247.
Mathew S, Abraham TE. Ferulic acid: an antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications[J]. Crit Rev Biotechnol, 2004, 24(2-3): 59-83.
Wong DW, Chan VJ, Batt SB, et al. Engineering saccharomyces cerevisiae to produce feruloyl esterase for the release of ferulic acid from switchgrass[J]. J Ind Microbiol Biotechnol, 2011, 38(12): 1961-1967.
Benoit I, Danchin EG, Bleichrodt RJ, et al. Biotechnological applications and potential of fungal feruloyl esterases based on prevalence, classification and biochemical diversity[J]. Biotechnol Lett, 2008, 30(3): 387-396.
Barone E, Calabrese V, Mancuso C. Ferulic acid and its therapeutic potential as a hormetin for age-related diseases[J]. Biogerontology, 2009, 10(2): 97-108.
Yagi K, Ohishi N. Action of ferulic acid and its derivatives as antioxidants[J]. J Nutr Sci Vitaminol (Tokyo), 1979, 25(2): 127-130.
Wang BH, Ou-Yang JP. Pharmacological actions of sodium ferulate in cardiovascular system[J]. Cardiovasc Drug Rev, 2005, 23(2): 161-172.
Jung KJ, Go EK, Kim JY, et al. Suppression of age-related renal changes in NF-kappaB and its target gene expression by dietary ferulate[J]. J Nutr Biochem, 2009, 20(5): 378-388.
Tsai FS, Wu LY, Yang SE, et al. Ferulic acid reverses the cognitive dysfunction caused by amyloid beta peptide 1-40 through anti-oxidant activity and cholinergic activation in rats[J]. Am J Chin Med, 2015, 43(2): 319-335.
Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging[J]. Cell, 2013, 153(6): 1194-1217.
Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging[J]. Proc Natl Acad Sci U S A,1993, 90(17): 7915-7922.
Zhang W, Zheng B, Deng N, et al. Effects of ethyl acetate fractional extract from Portulaca oleracea L. (PO-EA) on lifespan and healthspan in Caenorhabditis elegans[J]. J Food Sci, 2020, 85(12): 4367-4376.
Yang ZZ, Yu YT, Lin HR, et al. Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans[J]. Free Radic Biol Med, 2018, 129: 310-322.
Wang H, Liu J, Li T, et al. Blueberry extract promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans[J]. Food Funct, 2018,9(10): 5273-5282.
D'Archivio M, Filesi C, Di Benedetto R, et al. Polyphenols, dietary sources and bioavailability[J]. Ann Ist Super Sanita, 2007, 43(4): 348-361.
Barone E, Calabrese V, Mancuso C. Ferulic acid and its therapeutic potential as a hormetin for age-related diseases[J]. Biogerontology, 2009, 10(2): 97-108.
Kim DK, Jeon H, Cha DS. 4-Hydroxybenzoic acid-mediated lifespan extension in Caenorhabditis elegans[J]. J Functional Foods, 2014, 7: 630-640.
Kampkotter A, Gombitang NC, Zurawski RF, et al. Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans[J]. Arch Toxicol, 2007, 81(12): 849-858.
Tambara AL, de Los SML, Dal Forno AH, et al. Purple pitanga fruit (Eugenia uniflora L.) protects against oxidative stress and increase the lifespan in Caenorhabditis elegans via the DAF-16/FOXO pathway[J]. Food Chem Toxicol, 2018, 120: 639-650.
Song B, Wang H, Xia W, et al. Combination of apple peel and blueberry extracts synergistically induced lifespan extension via DAF-16 in Caenorhabditis elegans[J]. Food Funct, 2020, 11(7): 6170-6185.
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