Abstract

Aging is not a matter of choice; it is our fate. The “time-dependent functional decline that affects most living organisms” is coupled with several alterations in cellular processes, such as cell senescence, epigenetic alterations, genomic instability, stem cell exhaustion, among others. Age-related morphological changes in dental follicles have been investigated for decades, mainly motivated by the fact that cysts and tumors may arise in association with unerupted and/or impacted teeth. The more we understand the physiology of dental follicles, the more we are able to contextualize biological events that can be associated with the occurrence of odontogenic lesions, whose incidence increases with age. Thus, our objective was to assess age-related changes in metabolic pathways of dental follicles associated with unerupted/impacted mandibular third molars from young and adult individuals. For this purpose, a convenience sample of formalin-fixed paraffin-embedded (FFPE) dental follicles from young (<16 y.o., n = 13) and adult (>26 y.o., n = 7) individuals was selected. Samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based untargeted metabolomics. Multivariate and univariate analyses were conducted, and the prediction of altered pathways was performed by mummichog and Gene Set Enrichment Analysis (GSEA) approaches. Dental follicles from young and older individuals showed differences in pathways related to C21-steroid hormone biosynthesis, bile acid biosynthesis, galactose metabolism, androgen and estrogen biosynthesis, starch and sucrose metabolism, and lipoate metabolism. We conclude that metabolic pathways differences related to aging were observed between dental follicles from young and adult individuals. Our findings support that similar to other human tissues, dental follicles associated with unerupted tooth show alterations at a metabolic level with aging, which can pave the way for further studies on oral pathology, oral biology, and physiology.

Highlights

  • Dental follicles, referred to as dental sacs, comprise a defined structure with a remarkable role in periodontogenesis and tooth eruption [1,2,3,4]

  • We aimed to provide a list of predicted altered pathways, which can pave the way for further research that may use dental follicles/dental sacs as a model to understand aging, tooth eruption, bone physiology, and epithelium-mesenchymal interactions, as well as other phenomena that can be assessed in this peculiar tissue

  • We originally intended to have equal numbers of samples in both groups, samples from dental follicles of older patients were difficult to obtain, as most of the surgical procedures to remove unerupted thirds molars occur in adolescents

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Summary

Introduction

Referred to as dental sacs, comprise a defined structure with a remarkable role in periodontogenesis and tooth eruption [1,2,3,4]. Some pathological changes are described in this context, and are often agedependent, as in the case of squamous and mucous cell metaplasia/prosoplasia They involve molecular changes, such as increased expression of cell proliferation markers and lower expression of pro-apoptotic markers, mainly attributed to the epithelial component of this dental sac [8,9,10,11,12]. Some of these molecular and morphological alterations are considered as early signs of events that give rise to odontogenic lesions, such as developmental cysts and tumors. This is known to be a rare event [13]

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