Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells

Yamahara, Kohei; Yamamoto, Norio; Nakagawa, Takayuki; Ito, Juichi

doi:10.1016/j.heares.2015.04.009

Cited by 51 publications

(42 citation statements)

References 99 publications

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“…Finally, we measured total IGF-1 levels, which are considered a crude estimate of the biologically active hormone, whereas free IGF-1, which represents less than 1% of total IGF-1, is believed to be the most active form and to have greater physiological and clinical relevance than total IGF-1 41 . However, results from animal studies showing a role in the development and maintenance of hearing function also measured total IGF-1 16, 17 , and total IGF-1 has been used as a biomarker in most epidemiological studies in relation to chronic disease 15 .…”

Section: Discussionmentioning

confidence: 99%

“…Lower levels of IGF-1 have been shown to be associated with elevated rates of cardiovascular disease 15 . Second, molecular data from animal studies suggest a role for IGF-1 in the development and protection of hearing function 16, 17 . Rescue of hair cells from apoptosis via IGF-1 receptor-mediated actions or by downregulation of pro-apoptotic gene expression, and regulation of glucose transporters in the outer cells have been proposed as underlying mechanisms 18 .…”

Section: Introductionmentioning

confidence: 99%

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Insulin-like Growth Factor 1 in relation to future hearing impairment: findings from the English Longitudinal Study of Ageing

Lassale

Batty

Steptoe

et al. 2017

Sci Rep

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Insulin-like Growth Factor 1 (IGF-1) is associated with cardiovascular disease, itself a risk factor for hearing impairment, and, in animal studiesafter adjustment for a range of potential confounders. Among people ≥60 y (n = 2990) there was a nonsignificant 'J'-shaped association. Our observational evidence that higher levels of IGF-1 appeared to confer some protection against hearing impairment in some older adults warrants replication in other prospective cohort studies.Age-related hearing loss (presbycusis) is the most common cause of adult auditory deficiency and it is a major cause of disability 1, 2 . For example, in the United States 3 and in the United Kingdom 4 , around two-thirds of people older than 70 years report hearing loss. As well as being an important disease entity in its own right, it has marked economic, social, and health ramifications. Thus, poor hearing has a deleterious impact on physical functioning 5 , cognitive functioning 6 , social and family life 7 and mental health 8 . In the US, aggregate societal costs, including not only medical and assistive device costs but also reduced work productivity, were estimated to be $4.6 billion over the lifetime of affected people 9 . With the condition essentially incurable, the focus becomes identification of potentially modifiable risk factors.Evidence from a range of scientific disciplines implicates Insulin-like Growth Factor 1 (IGF-1) in the aetiology of hearing loss. First, atherosclerosis 10, 11 and selected cardiovascular disease risk factors -smoking 12 , diabetes 13 , overweight 12, 14 -have been associated with hearing impairment both in cross-sectional 11, 13, 14 and longitudinal studies 10,12 . Lower levels of IGF-1 have been shown to be associated with elevated rates of cardiovascular disease 15 . Second, molecular data from animal studies suggest a role for IGF-1 in the development and protection of hearing function 16,17 . Rescue of hair cells from apoptosis via IGF-1 receptor-mediated actions or by downregulation of pro-apoptotic gene expression, and regulation of glucose transporters in the outer cells have been proposed as underlying mechanisms 18 . Third, we have recently shown that physical stature, which is related to IGF-1 levels 19,20 , is related to hearing impairment 21 , with taller individuals less likely to experience hearing loss, which is consistent with results of two other studies 22,23 . While lower height in itself is of course not a risk factor for hearing impairment, the pre-adult characteristics that it proxies -inadequate nutrition, illness and poverty -may be.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin-like Growth Factor 1 in relation to future hearing impairment: findings from the English Longitudinal Study of Ageing

Lassale

Batty

Steptoe

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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“…In contrast, avian hair cell differentiation is potentiated by antagonists of BMP4 (19) and NOTCH (20) signaling. To facilitate mammalian hair cell regeneration, multiple candidate pathways are under investigation, including NOTCH (21), FGF22 (22), WNT (23), SHH (24), and IGF1 (25). IGF1 has been proposed as a factor for restoring auditory function in mammals (26).…”

Section: Introductionmentioning

confidence: 99%

ERBB2 is a Key Mediator in Hearing Restoration in Noise-Deafened Young Adult Mice

Zhang

Beaulac

et al. 2019

Preprint

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Noise induced hearing loss (NIHL) affects over ten million adults in the United States, and there is no biological treatment to restore endogenous function after damage. We hypothesized that activation of signaling from ERBB2 receptors in cochlear supporting cells could mitigate NIHL damage. We used the Tet-On genetic expression system to drive a constitutively active variant of ERBB2 (CA-ERBB2) in cochlear supporting cells three days after permanent noise damage in young adult mice. Hearing thresholds were assessed with auditory brainstem response tests prior to noise damage, and hearing recovery was assessed over a three month period. We evaluated supporting cell proliferation, inner and outer hair cell (IHC and OHC) survival, synaptic preservation, and IHC cytoskeletal alterations with histological techniques. Mice harboring CA-ERBB2 capability had similar hearing thresholds to control littermates prior to and immediately after noise exposure, and incurred similar levels of permanent hearing loss. Two and three months after noise exposure, CA-ERBB2+ mice demonstrated a partial but significant reversal of NIHL threshold shifts at the lowest frequency tested, out of five frequencies (n=19 total mice, p=0.0015, ANOVA). We also observed improved IHC and OHC survival (n=7 total cochleae, p=5 x 10 -5 , Kruskal-Wallis rank sum test). There was no evidence for sustained supporting cell proliferation. Some mortality was associated with doxycycline and furosemide treatments to induce the Tet-ON system. These data suggest that ERBB2 signaling in supporting cells promotes HC repair and some functional recovery. Funded by NIH R01 DC014261, and grants from the Schmitt Foundation and UR Ventures.

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“…IGF1 is a protein involved in neurogenesis and cell survival. It is important in the development and function of cells throughout the body, including cells of the inner ear, and in maintaining neuronal functioning . A cohort study of aging adults found higher levels of IGF1 were associated with decreased risk of HI after 6 years of follow‐up among participants 50 to 60 years of age at baseline, although this relationship did not exist in the cohort as a whole when those greater than 60 years of age were included .…”

Section: Introductionmentioning

confidence: 99%

“…It is important in the development and function of cells throughout the body, including cells of the inner ear, and in maintaining neuronal functioning. [14][15][16][17] A cohort study of aging adults found higher levels of IGF1 were associated with decreased risk of HI after 6 years of follow-up among participants 50 to 60 years of age at baseline, although this relationship did not exist in the cohort as a whole when those greater than 60 years of age were included. 18 In mouse models, deficiency of IGF1 was associated with worse hearing characterized by cochlear neuronal loss, delayed transmission in the central auditory pathway, and premature degeneration of the stria vascularis.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective factors and incident hearing impairment in the epidemiology of hearing loss study

et al. 2019

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Objective Hearing impairment (HI) is common in aging adults. Aldosterone, insulin‐like growth factor (IGF1), and brain‐derived neurotrophic factor (BDNF) have been identified as potentially protective of hearing. The present study aims to investigate these relationships. Methods The Epidemiology of Hearing Loss Study is a longitudinal population‐based study of aging in Beaver Dam, Wisconsin, that began in 1993. Baseline for the present investigation is the 1998 to 2000 phase. Follow‐up exams occurred approximately every 5 years, with the most recent occurring from 2013 to 2016. Hearing was measured by pure‐tone audiometry. HI was defined as a pure tone average (PTA) > 25 decibels hearing level in either ear. Change in PTA was the difference between follow‐up examinations and baseline. Baseline serum samples were used to measure biomarkers in 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the effect of biomarker levels in the lowest quintile (Q1) versus the highest (Q5) on incident HI and PTA change. Results There were 1,088 participants (69.3% women) at risk of HI included in analyses. The mean baseline age was 63.8 years (standard deviation = 7.0). The 16‐year incidence of HI was 54.9% and was higher in men (61.1%) than women (52.1%). In age‐ and sex‐adjusted models, aldosterone (HR = 1.06, 95% CI = 0.82–1.37), IGF1 (HR = 0.92, 95% CI = 0.71–1.19), and BDNF (HR = 0.86, 95% CI = 0.66–1.12) levels were not associated with risk of HI. PTA change was similarly not affected by biomarker levels. Conclusion Aldosterone, IGF1, and BDNF were not associated with decreased risk of age‐related hearing loss in this study. Level of Evidence 2b Laryngoscope, 129:2178–2183, 2019

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Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells

Cited by 51 publications

References 99 publications

Insulin-like Growth Factor 1 in relation to future hearing impairment: findings from the English Longitudinal Study of Ageing

Insulin-like Growth Factor 1 in relation to future hearing impairment: findings from the English Longitudinal Study of Ageing

ERBB2 is a Key Mediator in Hearing Restoration in Noise-Deafened Young Adult Mice

Neuroprotective factors and incident hearing impairment in the epidemiology of hearing loss study

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