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

Abstract

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.

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

“…Achieving an age of 58 to 73 years, the age of their participants, without other exposures known to increase risk of hearing loss may indicate that these participants represent a very different group from the EHLS and the U.S. population in general. The findings of Lassale et al 18 were for a specific age group in their population, and these results similarly may not be applicable to the general population. In the present study, in a similar age group of 53 to 59 years, a relationship between IGF1 and hearing was not observed.…”

“…In previous studies, higher serum aldosterone was shown to have a cross‐sectional relationship to lower hearing thresholds, better performance on HINTs, and was protective in animal models . Higher levels of IGF1 were shown to decrease incident HI among those 50 to 60 years of age in a longitudinal cohort, and low levels proved detrimental to hearing in animal models . BDNF has been suggested as a possible treatment for deafness and was effective in treatment of ototoxic and noise‐induced deafness in animal models .…”

“…[9][10][11][12][13] Higher levels of IGF1 were shown to decrease incident HI among those 50 to 60 years of age in a longitudinal cohort, and low levels proved detrimental to hearing in animal models. [18][19][20] BDNF has been suggested as a possible treatment for deafness and was effective in treatment of ototoxic and noise-induced deafness in animal models. 23,24,27 The potentially neuroprotective effects of aldosterone, IGF1, and BDNF demonstrated in previous studies were not replicated in this study.…”

“…[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. 19,20 BDNF is involved in neurogenesis, synaptic transmission, and cell survival.…”

“…If the findings of Tadros et al and Lassale et al, which are that serum aldosterone and IGF-1 are related to reduced risk of agerelated hearing loss, can be confirmed in another population, the applications and impact of these findings would be widespread. 9,18 The current study aims to investigate the potential relationships between these biomarkers and changes in hearing in a population-based cohort of older adults.…”