Chronic Inflammation and Age-Related Hearing: Based on Mendelian Randomization

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2024 Nov 21

PMID 39569023

Authors

Yan Wang

He Zhao

Kun Zhao

Huhuifen He

Xinyu Li

Jingjing Qiu

Limei Cui

Liang Chen

Wenjing Shang

Yan Sun

Affiliations

Soon will be listed here.

Abstract

Introduction: Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality.

Methods: Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL.

Results: Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL.

Discussion: This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research.

References

Bowl M, Dawson S . Age-Related Hearing Loss. Cold Spring Harb Perspect Med. 2018; 9(8). PMC: 6671929. DOI: 10.1101/cshperspect.a033217. View

Frosolini A, Franz L, Daloiso A, Lovato A, de Filippis C, Marioni G . Digging into the Role of Inflammatory Biomarkers in Sudden Sensorineural Hearing Loss Diagnosis and Prognosis: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2022; 58(7). PMC: 9324865. DOI: 10.3390/medicina58070963. View

Verschuur C, Agyemang-Prempeh A, Newman T . Inflammation is associated with a worsening of presbycusis: evidence from the MRC national study of hearing. Int J Audiol. 2014; 53(7):469-75. DOI: 10.3109/14992027.2014.891057. View

Verbanck M, Chen C, Neale B, Do R . Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018; 50(5):693-698. PMC: 6083837. DOI: 10.1038/s41588-018-0099-7. View

Rosa M, Chignon A, Li Z, Boulanger M, Arsenault B, Bosse Y . A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity. NPJ Genom Med. 2019; 4:23. PMC: 6754413. DOI: 10.1038/s41525-019-0097-4. View

Keithley E . Pathology and mechanisms of cochlear aging. J Neurosci Res. 2019; 98(9):1674-1684. PMC: 7496655. DOI: 10.1002/jnr.24439. View

Verschuur C, Dowell A, Syddall H, Ntani G, Simmonds S, Baylis D . Markers of inflammatory status are associated with hearing threshold in older people: findings from the Hertfordshire Ageing Study. Age Ageing. 2011; 41(1):92-7. DOI: 10.1093/ageing/afr140. View

Watson N, Ding B, Zhu X, Frisina R . Chronic inflammation - inflammaging - in the ageing cochlea: A novel target for future presbycusis therapy. Ageing Res Rev. 2017; 40:142-148. PMC: 5675822. DOI: 10.1016/j.arr.2017.10.002. View

Fransen K, Pettersson C, Hurtig-Wennlof A . CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study. BMC Cardiovasc Disord. 2022; 22(1):170. PMC: 9013148. DOI: 10.1186/s12872-022-02610-z. View

10.

Seicol B, Lin S, Xie R . Age-Related Hearing Loss Is Accompanied by Chronic Inflammation in the Cochlea and the Cochlear Nucleus. Front Aging Neurosci. 2022; 14:846804. PMC: 8995794. DOI: 10.3389/fnagi.2022.846804. View

11.

Delanghe J, Speeckaert R, Speeckaert M . Complement C3 and its polymorphism: biological and clinical consequences. Pathology. 2013; 46(1):1-10. DOI: 10.1097/PAT.0000000000000042. View

12.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

13.

Zhou T, Chen M, Yuan Z, Xia Z, Zhang S, Zhang Z . Inflammatory markers and the risk of idiopathic sudden sensorineural hearing loss: A Mendelian randomization study. Front Neurol. 2023; 14:1111255. PMC: 9992207. DOI: 10.3389/fneur.2023.1111255. View

14.

Sun B, Maranville J, Peters J, Stacey D, Staley J, Blackshaw J . Genomic atlas of the human plasma proteome. Nature. 2018; 558(7708):73-79. PMC: 6697541. DOI: 10.1038/s41586-018-0175-2. View

15.

Masuda M, Kanzaki S, Minami S, Kikuchi J, Kanzaki J, Sato H . Correlations of inflammatory biomarkers with the onset and prognosis of idiopathic sudden sensorineural hearing loss. Otol Neurotol. 2012; 33(7):1142-50. DOI: 10.1097/MAO.0b013e3182635417. View

16.

Wu T, Zhou J, Qiu J, Song Y, Guo W, Cui L . Tumor necrosis factor-α mediated inflammation versus apoptosis in age-related hearing loss. Front Aging Neurosci. 2022; 14:956503. PMC: 9491822. DOI: 10.3389/fnagi.2022.956503. View

17.

Stucky S, Wolf K, Kuo T . The economic effect of age-related hearing loss: national, state, and local estimates, 2002 and 2030. J Am Geriatr Soc. 2010; 58(3):618-9. DOI: 10.1111/j.1532-5415.2010.02746.x. View

18.

Xue Y, Zeng X, Tu W, Zhao J . Tumor Necrosis Factor-: The Next Marker of Stroke. Dis Markers. 2022; 2022:2395269. PMC: 8898850. DOI: 10.1155/2022/2395269. View

19.

Lopez-Castejon G, Brough D . Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011; 22(4):189-95. PMC: 3714593. DOI: 10.1016/j.cytogfr.2011.10.001. View

20.

Skrivankova V, Richmond R, Woolf B, Yarmolinsky J, Davies N, Swanson S . Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement. JAMA. 2021; 326(16):1614-1621. DOI: 10.1001/jama.2021.18236. View