Klotho-related Molecules Upregulated by Smoking Habit in Apparently Healthy Men: A Cross-sectional Study

Overview

Journal Sci Rep

Specialty Science

Date 2015 Sep 19

PMID 26382974

Citations 25

Authors

Kaori Nakanishi

Makoto Nishida

Masaya Harada

Tohru Ohama

Noritaka Kawada

Masaaki Murakami

Toshiki Moriyama

Keiko Yamauchi-Takihara

Affiliations

Soon will be listed here.

Abstract

While aging is unavoidable, the aging mechanism is still unclear because of its complexity. Smoking causes premature death and is considered as an environmental aging accelerator. In the present study, we focused on the influence of smoking to the serum concentration of anti-aging protein α-klotho (αKl) and the β-klotho-associated protein fibroblast growth factor (FGF)-21 in men. Subjects consisted of apparently healthy men over 40 years of age who underwent health examination. Physical and biochemical parameters, including the levels of several cytokines and growth factors, were obtained from the subjects. Among middle-aged men (46.1 ± 5.1 years), serum levels of FGF-21, soluble αKl (sαKl), and inflammation-related cytokine interleukin (IL)-6 were significantly higher in smokers than in never-smokers. Serum levels of FGF-21 increased and correlated with alanine transaminase, γ guanosine-5'-triphosphate, and total cholesterol only in smokers, suggesting FGF-21 as a metabolic disorder-related factor in smokers. In aged men (60.3 ± 1.7 years), although the serum levels of sαKl in never-smokers were low, smokers showed highly increased serum levels of sαKl. Serum levels of sαKl was correlated with IL-6 in middle-aged never-smokers, suggesting sαKl regulates IL-6. However, this correlation was disrupted in smokers and aged men.

Citing Articles

Serum Klotho Is Elevated in Patients with Acute Myocardial Infarction and Could Predict Poor In-Hospital Prognosis.

Pei Y, Huang W, Cao L, Yang F, Chi C, Zhu J J Cardiovasc Dev Dis. 2024; 11(9).

PMID: 39330350 PMC: 11432139. DOI: 10.3390/jcdd11090292.

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice.

Shanehbandpour-Tabari F, Gholamnataj F, Neamati N, Zabihi E, Feizi F, Parsian H Iran J Pharm Res. 2024; 23(1):e142903.

PMID: 39108652 PMC: 11302437. DOI: 10.5812/ijpr-142903.

Changes in metabolic hormones and trace elements in CSF in active smokers indicate oxidative damage to brain cells.

Zheng P, Wang F, Li H, Chen H, Li M, Ma H Endocr Connect. 2024; 13(6).

PMID: 38688314 PMC: 11227062. DOI: 10.1530/EC-24-0016.

Association between smoking, smoking cessation and serum α-klotho levels among American adults: National Health and Nutrition Examination Survey.

Liu T, Song M, Li J, Zhao Y, Zhong W PLoS One. 2024; 19(3):e0300562.

PMID: 38498398 PMC: 10947634. DOI: 10.1371/journal.pone.0300562.

Patients with central serous chorioretinopathy have high circulating alpha-klotho concentrations.

Tahara E, Yamamoto Y, Sugisawa T, Gomi F PLoS One. 2023; 18(12):e0295795.

PMID: 38127892 PMC: 10734912. DOI: 10.1371/journal.pone.0295795.

References

Pace T, Mletzko T, Alagbe O, Musselman D, Nemeroff C, Miller A . Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry. 2006; 163(9):1630-3. DOI: 10.1176/ajp.2006.163.9.1630. View

Harada M, Kamimura D, Arima Y, Kohsaka H, Nakatsuji Y, Nishida M . Temporal expression of growth factors triggered by epiregulin regulates inflammation development. J Immunol. 2015; 194(3):1039-46. DOI: 10.4049/jimmunol.1400562. View

Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt K, Goetz R . BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci U S A. 2007; 104(18):7432-7. PMC: 1855074. DOI: 10.1073/pnas.0701600104. View

Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A . alpha-Klotho as a regulator of calcium homeostasis. Science. 2007; 316(5831):1615-8. DOI: 10.1126/science.1135901. View

Lin B, Wang M, Blackmore C, Desnoyers L . Liver-specific activities of FGF19 require Klotho beta. J Biol Chem. 2007; 282(37):27277-27284. DOI: 10.1074/jbc.M704244200. View

Haack M, Sanchez E, Mullington J . Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep. 2007; 30(9):1145-52. PMC: 1978405. DOI: 10.1093/sleep/30.9.1145. View

Nicita-Mauro V, Lo Balbo C, Mento A, Nicita-Mauro C, Maltese G, Basile G . Smoking, aging and the centenarians. Exp Gerontol. 2007; 43(2):95-101. DOI: 10.1016/j.exger.2007.06.011. View

Scaldaferri F, Vetrano S, Sans M, Arena V, Straface G, Stigliano E . VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology. 2008; 136(2):585-95.e5. DOI: 10.1053/j.gastro.2008.09.064. View

Yoo S, Yoon H, Kim H, Chae C, De Falco S, Cho C . Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: a link between angiogenesis and inflammation. Arthritis Rheum. 2009; 60(2):345-54. DOI: 10.1002/art.24289. View

10.

Maekawa Y, Ishikawa K, Yasuda O, Oguro R, Hanasaki H, Kida I . Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation. Endocrine. 2009; 35(3):341-6. DOI: 10.1007/s12020-009-9181-3. View

11.

Li H, Bao Y, Xu A, Pan X, Lu J, Wu H . Serum fibroblast growth factor 21 is associated with adverse lipid profiles and gamma-glutamyltransferase but not insulin sensitivity in Chinese subjects. J Clin Endocrinol Metab. 2009; 94(6):2151-6. DOI: 10.1210/jc.2008-2331. View

12.

Sunyer J, Forastiere F, Pekkanen J, Plana E, Kolz M, Pistelli R . Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers. Nicotine Tob Res. 2009; 11(11):1347-53. DOI: 10.1093/ntr/ntp144. View

13.

Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y . Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects. Biochem Biophys Res Commun. 2010; 398(3):513-8. PMC: 4130489. DOI: 10.1016/j.bbrc.2010.06.110. View

14.

Kuro-O M . Klotho in health and disease. Curr Opin Nephrol Hypertens. 2012; 21(4):362-8. DOI: 10.1097/MNH.0b013e32835422ad. View

15.

Adcock I, Caramori G, Barnes P . Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration. 2011; 81(4):265-84. DOI: 10.1159/000324601. View

16.

Doi S, Zou Y, Togao O, Pastor J, John G, Wang L . Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011; 286(10):8655-8665. PMC: 3048747. DOI: 10.1074/jbc.M110.174037. View

17.

Sanada S, Nishida M, Ishii K, Moriyama T, Komuro I, Yamauchi-Takihara K . Smoking promotes subclinical atherosclerosis in apparently healthy men: 2-year ultrasonographic follow-up. Circ J. 2012; 76(12):2884-91. DOI: 10.1253/circj.cj-11-1506. View

18.

Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson R . 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013; 368(4):341-50. DOI: 10.1056/NEJMsa1211128. View

19.

Murakami M, Harada M, Kamimura D, Ogura H, Okuyama Y, Kumai N . Disease-association analysis of an inflammation-related feedback loop. Cell Rep. 2013; 3(3):946-59. DOI: 10.1016/j.celrep.2013.01.028. View

20.

Chow W, Xu A, Woo Y, Tso A, Cheung S, Fong C . Serum fibroblast growth factor-21 levels are associated with carotid atherosclerosis independent of established cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013; 33(10):2454-9. DOI: 10.1161/ATVBAHA.113.301599. View