Environmental exposure to polybrominated biphenyl (PBB) associates with an increased rate of biological aging.

Sarah W Curtis,M Elizabeth Marder,Carmen J Marsit,Varun Kilaru,Metrecia L Terrell,Dawayland O Cobb,Alicia K Smith,Dana Boyd Barr,Karen N Conneely,Michele Marcus

doi:10.18632/aging.102134

Abstract

Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants’ effect on aging.

Highlights

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals that are defined by their ability to disrupt the endocrine system by interfering with or mimicking endogenous hormone binding, synthesis, or transport [1]
Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration
These associations were consistent if PBB-153 was analyzed with each age acceleration measure (Figure S2), if total lipid level was not included in the model, or if age was included as an additional covariate (Table S2)

Summary

INTRODUCTION

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals that are defined by their ability to disrupt the endocrine system by interfering with or mimicking endogenous hormone binding, synthesis, or transport [1]. Positive age acceleration has been associated with advanced pubertal development (Tanner stages and age of menarche) [42, 43], as well as with earlier menopause [44] It is higher in breast tissue compared to blood [45], suggesting that hormonal factors like estrogen could be influencing the aging process. PBB levels have been associated with differences in DNA methylation proportions at sites enriched for estrogen signaling [59] Many of these health outcomes are sex-specific, and people who were exposed when they were younger have been found to be www.aging-us.com more vulnerable than those exposed when they were older [9, 11, 60,61,62]. We tested if age at exposure or sex would interact with PBB exposure to predict increased age acceleration, similar to other health outcomes reported with PBB exposure

RESULTS

DISCUSSION

MATERIALS AND METHODS