Barbara Ghinassi
Maria R. Matarazzo
Annalisa Di Ruscio- 1Anatomy and Cell Differentiation Lab, Department of Medicine and Aging Sciences, “G. D’Annunzio”University of Chieti—Pescara, Chieti, Italy
- 2Institute of Genetics and Biophysics Adriano Buzzati Traverso, (IGB-ABT) CNR, Naples, Italy
- 3Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA, United States
- 4Department of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
Editorial on the Research Topic
DNA methylation: The aging clock
One of the most fascinating biological questions is “why do we age?” Chronological age is not a reliable measure to assess the aging process. To understand and control aging, we need tools and approaches to evaluate biological age. A plethora of studies in both human and murine models have shown that aging is associated with changes in DNA methylation, a key epigenetic signature implicated in the regulation of gene expression. More recently, the definition of the “epigenetic clocks” - a set of CpG sites, the DNA methylation levels of which can be used to measure subject age - has unveiled novel molecular markers to monitor aging and assess a more accurate “epigenetic age”.
This Research Topic contributed to elucidating the role of DNA methylation and gene expression as a measure to understand and decipher aging in various disease contexts.
It is widely accepted that multiple environmental exposures and lifestyle factors, including obesity, can accelerate epigenetic aging, thus leading to an increased risk of age-related metabolic diseases (de Toro-Martín et al., 2019; Nannini et al., 2019; Fiorito et al., 2021; Etzel et al., 2022). Franzago et al. deeply review the interaction between epigenetic aging and obesity, emphasizing how the epigenome may serve as an intriguing target for age-related physiological changes and how its modification could influence aging and prolong a healthy lifespan. In particular, the authors focus on DNA methylation age as a clinical biomarker and on the potential reversal of epigenetic age using a personalized diet- and lifestyle-guided intervention (Franzago et al.).
Song et al. carry out an integrated analysis utilizing gene expression and DNA methylation microarrays in the temporal cortex of Alzheimer’s disease (AD) patients to further identify aberrantly methylated genes and define the molecular processes related to AD. Aging is a major risk factor for AD, the most prevalent cause of dementia, characterized by abnormal deposition of amyloid-β (Aβ) plaques and tau tangles in the brain associated with cognitive impairment. Several studies demonstrated that abnormally methylated genes have critical roles during AD neuropathology (Hass et al., 2009; Sanchez-Mut et al., 2014). Therein, the authors present numerous deregulated genes that are significantly enriched in biological processes such as cell morphogenesis, chemical synaptic transmission, and regulation of Aβ formation. In particular, they observe reduced methylation levels and increased TGFBR3 expression associated with Aβ accumulation. The authors suggest TGFBR3 might promote Aβ production by enhancing ß- and γ-secretase activities and propose TGFBR3 as a risk diagnostic biomarker and a therapeutic target for AD treatment (Song et al.).
Finally, Liu et al. investigate the impact of ethnicity on DNA methylation changes in peripheral blood cells from breast cancer (BC) patients. Age is one of the strongest risk factors for the development of BC, and evidence shows accelerated epigenetic aging in normal breast tissues adjacent to breast tumors in BC patients (Hofstatter et al., 2018; Rozenblit et al., 2022). DNA methylation signatures have been identified in the white blood cells as potential biomarkers for BC. In this writing, the authors identify relevant differences in the DNA methylation profiles when comparing European and Chinese populations. They report that BC is associated with altered methylation of CD160, ISYNA1, and RAD51B in the peripheral blood cells of European women, while an opposite profile is observed in the Chinese population. This may be due to genetic background or lifestyles and therefore warrant validation of epigenetic biomarkers in various ethnic groups (Liu et al.). However, large-scale prospective analyses will be needed to confirm the diagnostic and, or prognostic value of DNA methylation signatures in patients with BC, given the relatively small size of the analyzed case-control population.
In conclusion, by using different models and approaches, the studies presented in this Research Topic not only define DNA methylation as a tool to measure aging but identify this marker as a potential target to reverse age-related conditions, thereby reiterating the biological and clinical relevance of the DNA methylation to assess the aging process.
Author contributions
BG, MM and AD wrote the Editorial.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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References
de Toro-Martín, J., Guénard, F., Tchernof, A., Hould, F. S., Lebel, S., Julien, F., et al. (2019). Body mass index is associated with epigenetic age acceleration in the visceral adipose tissue of subjects with severe obesity. Clin. Epigenetics 11 (1), 172. doi:10.1186/s13148-019-0754-6
Etzel, L., Hastings, W. J., Hall, M. A., Heim, C. M., Meaney, M. J., Noll, J. G., et al. (2022). Obesity and accelerated epigenetic aging in a high-risk cohort of children. Sci. Rep. 12 (1), 8328. doi:10.1038/s41598-022-11562-5
Fiorito, G., Caini, S., Palli, D., Bendinelli, B., Saieva, C., Ermini, I., et al. (2021). DNA methylation-based biomarkers of aging were slowed down in a two-year diet and physical activity intervention trial: The DAMA study. Aging Cell 20 (10), e13439. doi:10.1111/acel.13439
Hass, M. R., Sato, C., Kopan, R., and Zhao, G. (2009). Presenilin: RIP and beyond. Semin. Cell Dev. Biol. 20, 201–210. doi:10.1016/j.semcdb.2008.11.014
Hofstatter, E., Horvath, S., Dalela, D., Gupta, P., Chagpar, A., Wali, V., et al. (2018). Increased epigenetic age in normal breast tissue from luminal breast cancer patients. Clin. Epigenet 10, 112. doi:10.1186/s13148-018-0534-8
Nannini, D. R., Joyce, B. T., Zheng, Y., Gao, T., Liu, L., Yoon, G., et al. (2019). Epigenetic age acceleration and metabolic syndrome in the coronary artery risk development in young adults study. Clin. Epigenetics 11 (1), 160, doi:10.1186/s13148-019-0767-1
Rozenblit, M., Hofstatter, E., Liu, Z., O'Meara, T., Storniolo, A. M., Dalela, D., et al. (2022). Evidence of accelerated epigenetic aging of breast tissues in patients with breast cancer is driven by CpGs associated with polycomb-related genes. Clin. Epigenet 14, 30 doi:10.1186/s13148-022-01249-z
Keywords: DNA methylation, epigenetic clock, aging, alzheimer disease, metabolic disorders, breast cancer
Citation: Ghinassi B, Matarazzo MR and Di Ruscio A (2023) Editorial: DNA methylation: The aging clock. Front. Cell Dev. Biol. 11:1164429. doi: 10.3389/fcell.2023.1164429
Received: 12 February 2023; Accepted: 13 February 2023;
Published: 15 March 2023.
Edited and reviewed by:
Michael E. Symonds, University of Nottingham, United KingdomCopyright © 2023 Ghinassi, Matarazzo and Di Ruscio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Barbara Ghinassi, Yi5naGluYXNzaUB1bmljaC5pdA==; Maria R. Matarazzo, bWFyaWEubWF0YXJhenpvQGlnYi5jbnIuaXQ=; Annalisa Di Ruscio, YWRpcnVzY2lAYmlkbWMuaGFydmFyZC5lZHU=