Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock

Sae-Lee, Chanachai; Corsi, Sarah; Barrow, Timothy M.; Kuhnle, Gunter Georg; Bollati, Valentina; Mathers, John C.; Byun, Hyang‐Min

doi:10.1002/mnfr.201800092

Cited by 79 publications

(58 citation statements)

References 39 publications

(62 reference statements)

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“…In a recent study, the effects of dietary supplementation with folic acid and vitamin B12 on epigenetic age deceleration were found dependent upon gender and MTHFR genotype (Sae-Lee et al 2018). Only the group of women with the MTHFR 677CC genotype displayed a deceleration in epigenetic aging upon vitaminic supplementation (Sae-Lee et al 2018).…”

Section: Discussionmentioning

confidence: 96%

One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project

et al. 2020

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Mediterranean diet has been proposed to promote healthy aging, but its effects on aging biomarkers have been poorly investigated. We evaluated the impact of a 1-year Mediterranean-like diet in a pilot study including 120 elderly healthy subjects from the NU-AGE study (60 Italians, 60 Poles) by measuring the changes in their epigenetic age, assessed by Horvath's clock. We observed a trend towards epigenetic rejuvenation of participants after nutritional intervention. The effect was statistically significant in the group of Polish females and in subjects who were epigenetically older at baseline. A genome-wide association study of epigenetic age changes after the intervention did not return significant (adjusted p value < 0.05) loci. However, we identified small-effect alleles (nominal p value < 10-4), mapping in genes enriched in pathways related to energy metabolism, regulation of cell cycle, and of immune functions. Together, these findings suggest that Mediterranean diet can promote epigenetic rejuvenation but with country-, sex-, and individual-specific effects, thus highlighting the need for a personalized approach to nutritional interventions.

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Section: Discussionmentioning

confidence: 96%

One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project

et al. 2020

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“…DNA methylation is reversible, therefore identification of aberrant DNA methylation patterns in genes critical to metabolic regulation may provide unique opportunities for intervention strategies. Lifestyle modifications such as diet ( Obeid et al, 2018 ; Sae-Lee et al, 2018 ) and exercise ( Rönn et al, 2013 ; Fabre et al, 2018 ) have been shown to reprogram altered DNA methylation, thus may lead to restoring metabolic homeostasis and preventing disease progression.…”

Section: Introductionmentioning

confidence: 99%

Ethnic and Adipose Depot Specific Associations Between DNA Methylation and Metabolic Risk

et al. 2020

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Background Metabolic risk varies according to body mass index (BMI), body fat distribution and ethnicity. In recent years, epigenetics, which reflect gene-environment interactions have attracted considerable interest as mechanisms that may mediate differences in metabolic risk. The aim of this study was to investigate DNA methylation differences in abdominal and gluteal subcutaneous adipose tissues of normal-weight and obese black and white South African women. Methods Body composition was assessed using dual-energy x-ray absorptiometry and computerized tomography, and insulin sensitivity was measured using a frequently sampled intravenous glucose tolerance test in 54 normal-weight (BMI 18–25 kg/m 2 ) and obese (BMI ≥ 30 kg/m 2 ) women. Global and insulin receptor ( INSR ) DNA methylation was quantified in abdominal (ASAT) and gluteal (GSAT) subcutaneous adipose depots, using the Imprint methylation enzyme-linked immunosorbent assay and pyrosequencing. INSR gene expression was measured using quantitative real-time PCR. Results Global DNA methylation in GSAT varied according to BMI and ethnicity, with higher levels observed in normal-weight white compared to normal-weight black ( p = 0.030) and obese white ( p = 0.012) women. Pyrosequencing of 14 CpG sites within the INSR promoter also showed BMI, adipose depot and ethnic differences, although inter-individual variability prevented attainment of statistical significance. Both global and INSR methylation were correlated with body fat distribution, insulin resistance and systemic inflammation, which were dependent on ethnicity and the adipose depot. Adipose depot and ethnic differences in INSR gene expression were observed. Conclusion We show small, but significant global and INSR promoter DNA methylation differences in GSAT and ASAT of normal-weight and obese black and white South African women. DNA methylation in ASAT was associated with centralization of body fat in white women, whereas in black women DNA methylation in GSAT was associated with insulin resistance and systemic inflammation. Our findings suggest that GSAT rather than ASAT may be a determinant of metabolic risk in black women and provide novel evidence that altered DNA methylation within adipose depots may contribute to ethnic differences in body fat distribution and cardiometabolic risk.

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“…Additionally, our results uncover novel machine-learned associations between age and specific metatranscriptomic features that could guide the design of nutritional interventions to reduce biological age and increase the human healthspan (see e.g. Sae-Lee et al, 2018;Ghosh et al, 2019). We will continue to evaluate and improve the models as we obtain more data.…”

Section: Resultsmentioning

confidence: 88%

An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging

Gopu

Cai

Krishnan

et al. 2020

Preprint

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Accurate measurement of the biological markers of the aging process could provide an “aging clock” measuring predicted longevity and allow for the quantification of the effects of specific lifestyle choices on healthy aging. Using modern machine learning techniques, we demonstrate that chronological age can be predicted accurately from (a) the expression level of human genes in capillary blood, and (b) the expression level of microbial genes in stool samples. The latter uses the largest existing metatranscriptomic dataset, stool samples from 90,303 individuals, and is the highest-performing gut microbiome-based aging model reported to date. Our analysis suggests associations between biological age and lifestyle/health factors, e.g., people on a paleo diet or with IBS tend to be biologically older, and people on a vegetarian diet tend to be biologically younger. We delineate the key pathways of systems-level biological decline based on the age-specific features of our model; targeting these mechanisms can aid in development of new anti-aging therapeutic strategies.

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Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock

Cited by 79 publications

References 39 publications

One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project

One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project

Ethnic and Adipose Depot Specific Associations Between DNA Methylation and Metabolic Risk

An accurate aging clock developed from the largest dataset of microbial and human gene expression reveals molecular mechanisms of aging

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