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

**Authors:** Kaori Nakanishi, Makoto Nishida, Masaya Harada, Tohru Ohama, Noritaka Kawada, Masaaki Murakami, Toshiki Moriyama, Keiko Yamauchi-Takihara

PMC · DOI: 10.1038/srep14230 · Scientific Reports · 2015-09-18

## TL;DR

This study found that smoking increases levels of certain anti-aging and inflammation-related proteins in healthy men, suggesting a link between smoking and accelerated aging.

## Contribution

The study reveals smoking's impact on α-klotho and FGF-21 levels, showing age-dependent differences in protein regulation.

## Key findings

- Smoking increases FGF-21, sαKl, and IL-6 levels in middle-aged men.
- FGF-21 correlates with metabolic markers only in smokers.
- Smoking disrupts the correlation between sαKl and IL-6 in middle-aged and older men.

## 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.

## Linked entities

- **Proteins:** FGF21 (fibroblast growth factor 21)

## Full-text entities

- **Genes:** EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, TNC (tenascin C) [NCBI Gene 3371] {aka 150-225, DFNA56, GMEM, GP, HXB, JI}, TGFA (transforming growth factor alpha) [NCBI Gene 7039] {aka TFGA}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, KLB (klotho beta) [NCBI Gene 152831] {aka BKL}, KL (klotho) [NCBI Gene 9365] {aka HFTC3, KLA}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Kl (klotho) [NCBI Gene 16591] {aka alpha-kl}, HBEGF (heparin binding EGF like growth factor) [NCBI Gene 1839] {aka DTR, DTS, DTSF, HEGFL}, Klb (klotho beta) [NCBI Gene 83379] {aka betaKlotho}, AREG (amphiregulin) [NCBI Gene 374] {aka AR, AREGB, CRDGF, SDGF}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, FGF19 (fibroblast growth factor 19) [NCBI Gene 9965], ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, BTC (betacellulin) [NCBI Gene 685], Fgf21 (fibroblast growth factor 21) [NCBI Gene 56636] {aka Fgf8c}, FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}
- **Diseases:** diseases (MESH:D004194), metabolic syndrome (MESH:D024821), aging-related diseases (MESH:D010024), pathologies (MESH:D005598), visceral fat accumulation (MESH:D004620), pulmonary disease (MESH:D008171), cardiovascular disease (MESH:D002318), hypertension (MESH:D006973), death (MESH:D003643), skin atrophy (MESH:D001284), hyperlipidemia (MESH:D006949), sleep deprivation (MESH:D012892), atherosclerosis (MESH:D050197), Smoking (MESH:D015208), ectopic calcification (MESH:D002114), inflammation (MESH:D007249), macular degeneration (MESH:D008268), COPD (MESH:D029424), non-alcoholic fatty liver (MESH:D065626), pulmonary emphysema (MESH:D011656), TC (MESH:C535937), Cancer (MESH:D009369), metabolic disorder (MESH:D008659)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4585559/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC4585559/full.md

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Source: https://tomesphere.com/paper/PMC4585559