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An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

ABSTRACT: Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.Trial Registration: Registry Name: ClincialTrials.Gov.Registration Number: NCT01302379.Date of Registration: February 2011.URL: https://clinicaltrials.gov/ct2/show/NCT01302379.

SUBMITTER: Nwanaji-Enwerem JC

PROVIDER: S-EPMC8684118 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

Nwanaji-Enwerem Jamaji C JC Chung Felicia Fei-Lei FF Van der Laan Lars L Novoloaca Alexei A Cuenin Cyrille C Johansson Harriet H Bonanni Bernardo B Hubbard Alan E AE Smith Martyn T MT Hartman Sheri J SJ Cardenas Andres A Sears Dorothy D DD Herceg Zdenko Z

Clinical epigenetics 20211217 1

Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P < 0.005). However, no significant epigenetic aging associations were obs ...[more]

PMID: 34920739

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Project description:BackgroundElevated body mass index (BMI) in breast cancer survivors (BCS) is associated with cancer recurrence and poorer treatment response. Guidelines recommend 5%-10% weight loss for overweight or obese BCS.ObjectivesTo assess effectiveness of lifestyle interventions for female BCS on weight loss, BMI, body composition, health-related quality of life (HRQoL), physical functioning, psychosocial measures, biomarkers.DesignSystematic review of reviews and meta-analyses.SettingAll clinical settings.ParticipantsAdult female BCS (active treatment or post-treatment).MethodsMedline, Embase, CINAHL, PsycINFO, Cochrane Library (including Database of Abstracts of Reviews of Effects) were searched for systematic reviews published in English between 1990 and 2022, with weight, BMI or body fat as primary outcome. Narrative reviews, editorials, letters, conference abstracts were excluded. Review quality was assessed using the Joanna Briggs Institute quality assessment tool.Results17 reviews were included. Twelve reported significant reductions in one or more anthropometric outcomes: weight -1.36 kg (95% CI:-2.51 to -0.21) to -3.8 kg (95% CI: -5.6 to -1.9); BMI -0.89 kg/m2 (95% CI: -0.15 to -0.28) to -3.59 kg/m2 (95% CI: -6.29 to 0.89) or body fat -1.6% (95% CI: -2.31 to -0.88) to -2.6% (95% CI not reported). Significant reductions in two or more anthropometric outcomes were reported in 7/12 reviews, with effective interventions comprising aerobic exercise/aerobic exercise plus resistance training (n=5), or diet and exercise with or without counselling (n=2). Significant improvements were also reported for HRQoL (8/11 reviews), mental health (4/7) and physical functioning (2/3). Group interventions comprising aerobic exercise or aerobic exercise plus resistance training were most likely to improve outcomes.ConclusionsLifestyle interventions can significantly improve outcomes for BCS. Multimodal interventions are likely to have the greatest impact in reducing weight, BMI and body fat. Further research must define the optimal combination, intensity and duration of effective interventions.Prospero registration numberCRD42021283481.

Project description:BackgroundLittle is known about the effect of intentional weight loss and subsequent weight regain on cardiometabolic risk factors in older adults. The objective of this study was to determine how cardiometabolic risk factors change in the year following significant intentional weight loss in postmenopausal women, and if observed changes were affected by weight and fat regain.MethodsEighty, overweight and obese, older women (age = 58.8±5.1 years) were followed through a 5-month weight loss intervention and a subsequent 12-month nonintervention period. Body weight/composition and cardiometabolic risk factors (blood pressure; total, high-density lipoprotein, and low-density lipoprotein cholesterol; triglycerides; fasting glucose and insulin; and Homeostatic Model Assessment of Insulin Resistance) were analyzed at baseline, immediately postintervention, and 6- and 12-months postintervention.ResultsAverage weight loss during the 5-month intervention was 11.4±4.1kg and 31.4% of lost weight was regained during the 12-month follow-up. On average, all risk factor variables were significantly improved with weight loss but regressed toward baseline values during the year subsequent to weight loss. Increases in total cholesterol, triglycerides, glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance during the postintervention follow-up were significantly (p < .05) associated with weight and fat mass regain. Among women who regained weight, model-adjusted total cholesterol (205.8±4.0 vs 199.7±2.9mg/dL), low-density lipoprotein cholesterol (128.4±3.4 vs 122.7±2.4mg/dL), insulin (12.6±0.7 vs 11.4±0.7mg/dL), and Homeostatic Model Assessment of Insulin Resistance (55.8±3.5 vs 50.9±3.7mg/dL) were higher at follow-up compared with baseline.ConclusionsFor postmenopausal women, even partial weight regain following intentional weight loss is associated with increased cardiometabolic risk. Conversely, maintenance of or continued weight loss is associated with sustained improvement in the cardiometabolic profile.

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An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

Publications

An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors.

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