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Oral. Health"],"abstract":"<jats:p>Aging is not a matter of choice; it is our fate. The \u201ctime-dependent functional decline that affects most living organisms\u201d 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 (&amp;lt;16 y.o., <jats:italic>n<\/jats:italic> = 13) and adult (&amp;gt;26 y.o., <jats:italic>n<\/jats:italic> = 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 <jats:italic>mummichog<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/froh.2021.677731","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T06:33:12Z","timestamp":1623997992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Age-Related Metabolic Pathways Changes in Dental Follicles: A Pilot Study"],"prefix":"10.3389","volume":"2","author":[{"given":"Victor Coutinho","family":"Bastos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica Gardone","family":"Vit\u00f3rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Rayra","family":"Martins-Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"Leite-Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri Abner Rocha","family":"Lebron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Rezende","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipe Fideles","family":"Duarte-Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tha\u00eds dos Santos Fontes","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilaine Val\u00e9ria de Souza","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lis\u00e9te Celina","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Nori de","family":"Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele Andr\u00e9 Baptista","family":"Canuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Cavali\u00e9ri","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Santiago","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1034\/j.1600-0757.2000.2240102.x","article-title":"Development and general structure of the periodontium","volume":"24","author":"Cho","year":"2000","journal-title":"Periodontol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1600-0714.1980.tb00377.x","article-title":"Tooth eruption: evidence for the central role of the dental follicle","volume":"9","author":"Cahill","year":"1980","journal-title":"J Oral Pathol Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3109\/03008209509013718","article-title":"The basic and applied biology of tooth eruption","volume":"32","author":"Marks","year":"1995","journal-title":"Connect Tissue Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e58803","DOI":"10.1371\/journal.pone.0058803","article-title":"Tooth eruption results from bone remodelling driven by bite forces sensed by soft tissue dental follicles: a finite element analysis","volume":"8","author":"Sarrafpour","year":"2013","journal-title":"PLoS ONE."},{"key":"B5","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/ar.1091700312","article-title":"The development of the periodontium. 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