Nanomechanical and Molecular Characterization of Aging in Dentinal Collagen

Abstract

Methylglyoxal (MGO) is an important molecule derived from glucose metabolism with the capacity of attaching to collagen and generating advanced glycation end products (AGEs), which accumulate in tissues over time and are associated with aging and diseases. However, the accumulation of MGO-derived AGEs in dentin and their effect on the nanomechanical properties of dentinal collagen remain unknown. Thus, the aim of the present study was to quantify MGO-based AGEs in the organic matrix of human dentin as a function of age and associate these changes with alterations in the nanomechanical and ultrastructural properties of dentinal collagen. For this, 12 healthy teeth from <26-y-old and >50-y-old patients were collected and prepared to obtain crown and root dentin discs. Following demineralization, MGO-derived AGEs were quantified with a competitive ELISA. In addition, atomic force microscopy nanoindentation was utilized to measure changes in elastic modulus in peritubular and intertubular collagen fibrils. Finally, principal component analysis was carried out to determine aging profiles for crown and root dentin. Results showed an increased presence of MGO AGEs in the organic matrix of dentin in the >50-y-old specimens as compared with the <26-y-old specimens in crown and root. Furthermore, an increase in peritubular and intertubular collagen elasticity was observed in the >50-y-old group associated with ultrastructural changes in the organic matrix as determined by atomic force microscopy analysis. Furthermore, principal component analysis loading plots suggested different “aging profiles” in crown and root dentin, which could have important therapeutic implications in restorative and adhesive dentistry approaches. Overall, these results demonstrate that the organic matrix of human dentin undergoes aging-related changes due to MGO-derived AGEs with important changes in the nanomechanical behavior of collagen that may affect diagnostic and restorative procedures in older people.

Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy

“…In this report, our AFM‐based technique was utilised to compare different regions of enamel across a small number of individuals from two different age groups, suggesting that older enamel may display particular ageing markers that could play an important role – for example – in restorative dentistry approaches. However, it is important to consider that changes in dental tissues associated to ageing are multifactorial, and may involve several molecular, mechanical and biological alterations over time 34 . Furthermore, individual differences must be considered when analysing the resulting data, particularly as the process of ageing is not uniform across individuals and may have important differences from a person‐to‐person basis.…”

“…However, it is important to consider that changes in dental tissues associated to ageing are multifactorial, and may involve several molecular, mechanical and biological alterations over time. 34 Furthermore, individual differences must be considered when analysing the resulting data, particularly as the process of ageing is not uniform across individuals and may have important differences from a person-to-person basis. Therefore, future work should focus on exploring the ageing of mineralised dental tissues -including enamelacross larger sample sizes in order to compensate for individual differences as well as other potential confounding factors such as behavioural habits and mechanical forces, among others.…”

Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy

“…In this report, our AFM-based technique was utilised to compare different regions of enamel across a small number of individuals from two different age groups, suggesting that older enamel may display particular ageing markers that could play an important role – for example - in restorative dentistry approaches. However, it is important to consider that changes in dental tissues associated to ageing are multifactorial, and may involve several molecular, mechanical, and biological alterations over time 32 . Furthermore, individual differences must be considered when analysing the resulting data, particularly as the process of ageing is not uniform across individuals and may have important differences from a person-to-person basis.…”

Nanoscale Dynamics of Streptococcal Adhesion to AGE-Modified Collagen

“…The aging process generates significant changes in tissues, including the time-dependent accumulation of AGEs. Among these, MGO-derived AGEs are biologically relevant in dentistry as they are known to accumulate in oral tissues such as dentin and periodontal ligament (Delle Monache et al 2021; Schuh et al 2022). Notably, the interaction of MGO with arginine residues in proteins including collagen induces formation of the clinically relevant AGE MG-H1.…”