Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging

Noreen, Faiza; Chaber-Ciopinska, Anna; Reguła, Jarosław; Schär, Primo; Truninger, Kaspar

doi:10.1186/s13148-020-00956-9

Cited by 5 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ncbi.nlm.nih.gov/geo" on November 9, 2020). The dataset is comprised of 124 normal cecum (proximal) and sigmoid (distal) colon mucosa biopsies from 31 healthy Polish women and was collected for a previous longitudinal analysis of aspirin use and epigenetic aging [14]. Colonoscopies with mucosa biopsies were performed on the women at baseline (T1) and during follow-up 10 years later (T2).…”

Section: Study Population and Data Collectionmentioning

confidence: 99%

“…The dataset also contained information on participant chronological ages, BMIs, DNA methylation batch, and if any type of polyps were observed on T1 or T2 colonoscopies (yes versus no). Additional details about study participants as well as informed consent and ethical conduct of study information regarding the collection of this data can be found in the original publication of the data [14].…”

Section: Study Population and Data Collectionmentioning

confidence: 99%

“…To date, blood epigenetic age acceleration (Horvath's pan-tissue metric [10]) has been associated with future colon cancer development [11], and survival associated epigenetic age acceleration (Horvath metric) has also been demonstrated in colon tumors [12]. Moreover, a more recent 10-year study of healthy colon tissue in Polish women reported epigenetic age deceleration (PhenoAge metric [13]) in the proximal colon of long-term aspirin users when compared to non-users [14]. Although these studies do take advantage of the most well-known epigenetic age measures, they do not include epigenetic aging measures that estimate cell divisions-otherwise known as "mitotic clocks."…”

Section: Introductionmentioning

confidence: 99%

“…Although these studies do take advantage of the most well-known epigenetic age measures, they do not include epigenetic aging measures that estimate cell divisions-otherwise known as "mitotic clocks." Understanding aspirin and CRC relationships with mitotic clocks is particularly important given that deviations from chronological age captured by many of the other epigenetic clocks are independent of cell proliferation [14]. This may result in the conclusion that aspirin's relationship with epigenetic aging processes is solely proliferation independent when this may not be the case.…”

Section: Introductionmentioning

confidence: 99%

“…In the present analysis, we utilize the aforementioned Polish healthy colon dataset [14] and explored relationships of long-term aspirin use with EpiTOC, EpiTOC2, and MiAge. Additionally, we take an inventory of existing CRC epigenetic aging studies and provide recommendations for future work in this area.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Nwanaji‐Enwerem

Nze

2021

Epigenetics Commun.

View full text Add to dashboard Cite

Background Despite the known role of mitosis in colorectal cancer, previous associations of long-term aspirin use with suppressed cancer-related epigenetic aging did not involve epigenetic mitotic clocks. We investigated these relationships using three epigenetic mitotic clocks developed for cancer risk prediction: EpiTOC, EpiTOC2, and MiAge. We utilized publicly available HumanMethylationEPIC BeadChip data from 112 healthy colon (proximal and distal) mucosal samples taken at baseline (T1) and at 10-years follow-up (T2) from a screening cohort of 28 Polish women (11 non-users and 17 long-term [≥ 2 years] aspirin users). Mitotic clock values were divided by chronological age at each timepoint to obtain intrinsic rates (IRs). We evaluated differences in residuals of the mitotic clock IRs taken from linear mixed effects models adjusted for BMI, polyp status, and DNA methylation batch. Findings EpiTOC, EpiTOC2, and MiAge were significantly correlated with chronological age (P < 0.05) with correlations ranging from 0.41 to 0.63. The EpiTOC, EpiTOC2, and MiAge clocks were strongly correlated with each other in proximal and distal samples (r > 0.79, P < 0.0001). We observed proximal within group median clock IR deceleration for EpiTOC (-0.0004 DNAm, P = 0.008), EpiTOC2 (− 16 cell divisions, P = 0.009), and MiAge (− 3 cell divisions, P = 0.002) for long-term aspirin users from T1 to T2 but not for non-users. In distal samples, only the long-term user MiAge IR was significantly deaccelerated (− 3 cell divisions, P = 0.009). Conclusions Our observed findings support previously reported longitudinal associations of aspirin use with deceleration of other epigenetic age measures in the proximal colon. Our mitotic clock results suggest that cell proliferation could play a role in some aspirin relationships with epigenetic aging. Furthermore, the findings provide added impetus for establishing gold standards for epigenetic aging and consensus guidelines for more comprehensive reporting in future epigenetic aging cancer studies.

show abstract

Section: Study Population and Data Collectionmentioning

confidence: 99%

Section: Study Population and Data Collectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Nwanaji‐Enwerem

Nze

2021

Epigenetics Commun.

View full text Add to dashboard Cite

show abstract

Map of epigenetic age acceleration: a worldwide meta-analysis

Yusipov,

Kalyakulina,

Franceschi

et al. 2024

Preprint

View full text Add to dashboard Cite

This study is the first systematic meta-analysis of epigenetic age acceleration of the largest publicly available DNA methylation data for healthy samples (93 datasets, 23K samples), focusing on geographic and ethnic aspects of different countries (25 countries) and populations (31 ethnicities) around the world. The most popular epigenetic tools for assessing age acceleration were examined in detail, their quality metrics were analyzed, and their ability to extrapolate to epigenetic data from different tissue types and age ranges different from the training data of these models was explored. In most cases, the models are not consistent with each other and show different signs of age acceleration, with the PhenoAge model tending to systematically underestimate and different versions of the GrimAge model tending to systematically overestimate the age prediction of healthy subjects. Although GEO is the largest open-access epigenetic database, most countries and populations are not represented, and different datasets use different criteria for determining healthy controls. Because of this, it is difficult to fully isolate the contribution of "geography/environment", "ethnicity" and "healthiness" to epigenetic age acceleration. However, the DunedinPACE metric, which measures aging rate, adequately reflects the standard of living and socioeconomic indicators in countries, although it can be applied only to blood methylation data. When comparing epigenetic age acceleration, males age faster than females in most of the countries and populations considered.

show abstract

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

et al. 2022

View full text Add to dashboard Cite

Common chronic diseases represent the greatest driver of rising healthcare costs, as well as declining function, independence, and quality of life. Geroscience-guided approaches seek to delay the onset and progression of multiple chronic conditions by targeting fundamental biological pathways of aging. This approach is more likely to improve overall health and function in old age than treating individual diseases, by addressing aging the largest and mostly ignored risk factor for the leading causes of morbidity in older adults. Nevertheless, challenges in repurposing existing and moving newly discovered interventions from the bench to clinical care have impeded the progress of this potentially transformational paradigm shift. In this article, we propose the creation of a standardized process for evaluating FDA-approved medications for their geroscience potential. Criteria for systematically evaluating the existing literature that spans from animal models to human studies will permit the prioritization of efforts and financial investments for translating geroscience and allow immediate progress on the design of the next Targeting Aging with MEtformin (TAME)-like study involving such candidate gerotherapeutics.

show abstract

Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging

Cited by 5 publications

References 37 publications

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Long-term aspirin use and epigenetic mitotic clocks for cancer risk prediction: findings in healthy colon mucosa and recommendations for future epigenetic aging studies

Map of epigenetic age acceleration: a worldwide meta-analysis

Geroscience‐guided repurposing of FDA‐approved drugs to target aging: A proposed process and prioritization

Contact Info

Product

Resources

About