Evidence map›Paper›PMID 40922554›Full record

Trial reportAging cell2025

Epigenetic Age Acceleration and Cardiometabolic Biomarkers in Response to Weight-Loss Dietary Interventions Among Obese Individuals: The MACRO Trial.

Minghao Kou, Xiang Li, Yoriko Heianza, Kirsten Dorans, Lydia Bazzano, Lu Qi

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Minghao KouDepartment of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.ORCID 0000-0002-3885-4103
Xiang LiDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA.ORCID 0000-0002-6637-6428
Yoriko HeianzaDepartment of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
Kirsten DoransDepartment of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
Lydia BazzanoDepartment of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.
Lu QiDepartment of Epidemiology, Celia Scott Weatherhead School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.

Funding

Tulane COBRE in Cardiometabolic Diseases Clinical Research CoreP20GM109036 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI Katherine Teresa Mills · 2016 to 2026
$25.3M
RISK FACTORS FOR CVD IN WOMENR01HL034594 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI JoAnn Elisabeth Manson, Lu Qi · 1985 to 2026
$13.8M
Nutrigenetics and Nutrigenomics for Precision Weight-Loss Diet InterventionsR01DK115679 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI Lu Qi · 2018 to 2026
$5.3M
Common Genetic Variation and Quantitative Diabetes TraitsR01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2008 to 2014
$5.0M
Genetic Markers of CHD in Type 2 DiabetesR01HL071981 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI QI, LU · 2003 to 2012
$4.9M
Obesity Genes, Energy Regulation in Response to Weight-Loss DietsR01DK091718 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI QI, LU · 2012 to 2021
$4.5M
Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut MicrobiotaR01DK100383 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI QI, LU · 2014 to 2024
$4.2M
TOPMed Omics of Type 2 Diabetes and Quantitative TraitsUM1DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MANNING, ALISA KNODLE · 2021 to 2025
$3.8M
Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Genome-wide interactions with diet patterns on long-term weight changeR21HL126024 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI QI, LU · 2015 to 2016
$421k
NHLBI NIH HHS HL034594NHLBI NIH HHS HL071981NHLBI NIH HHS HL126024NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL071981NHLBI NIH HHS R21 HL126024NIDDK NIH HHS DK078616NIDDK NIH HHS DK091718NIDDK NIH HHS DK100383NIDDK NIH HHS DK115679NIDDK NIH HHS R01 DK078616NIDDK NIH HHS R01 DK091718NIDDK NIH HHS R01 DK100383NIDDK NIH HHS R01 DK115679NIDDK NIH HHS U01 DK078616NIDDK NIH HHS UM1 DK078616NIGMS NIH HHS P20 GM109036
6 · The paper itself

Abstract

Epigenetic clocks have emerged as promising biomarkers of aging, but their responsiveness to lifestyle interventions and relevance for short-term changes in cardiometabolic health remain uncertain. In this study, we examined the associations between three epigenetic aging measures (DunedinPACE, PCPhenoAge acceleration, and PCGrimAge acceleration) and a broad panel of cardiometabolic biomarkers in 144 obese participants from the MACRO trial, a 12-month weight-loss dietary intervention comparing low-carbohydrate and low-fat diets. At pre-intervention baseline, DunedinPACE was significantly associated with several cardiometabolic biomarkers (FDR [false discovery rate] < 0.05), including insulin, homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, adiponectin, and ghrelin. These associations were substantially attenuated following the intervention, with only CRP and adiponectin remaining significant. Changes in epigenetic aging measures were not significantly associated with changes in biomarkers, nor did they mediate the effects of weight loss. Our findings highlight DunedinPACE as a sensitive biomarker of cardiometabolic health in adults with obesity but raise questions about the utility of epigenetic clocks as causal targets in short-term lifestyle interventions. While caloric restriction may attenuate some phenotypic manifestations of biological aging, short-term changes in epigenetic aging measures may not fully reflect underlying cardiometabolic changes. These results underscore the need for caution in interpreting epigenetic aging as a modifiable intervention target.

Indexed as

AgingBiomarkersEpigenesis, GeneticObesityWeight LossAdultFemaleHumansMaleMiddle AgedBiomarkersagingcardiometabolic healthdietary interventionDNA methylation

Identifiers

PMID40922554
PMCPMC12611269

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.