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Table 1 Estimated difference in epigenetic age biomarkers after 6 months of metformin and weight loss program interventions compared to placebo (N = 192)

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

Aging biomarker models Weight loss only (N = 48) Metformin only (N = 48) Weight loss plus metformin (N = 48)
difference in DNA methylation biomarker (95% CI) P Difference in DNA methylation biomarker (95% CI) P difference in DNA methylation biomarker (95% CI) P
EAA Hannum units: years
Unadjusted Intent to Treat 1.13 (− 0.46, 2.73) 0.16 0.25 (− 1.35, 1.84) 0.76 1.05 (− 0.55, 2.64) 0.20
Adjusted Intent to Treat 0.98 (− 0.48, 2.44) 0.19 0.47 (− 0.98, 1.91) 0.53 0.45 (− 1.04, 1.95) 0.55
Unadjusted High Adherence* 1.03 (− 0.95, 3.02) 0.30 0.43 (− 1.29, 2.16) 0.62 1.35 (− 0.58, 3.28) 0.17
Adjusted High Adherence* − 0.04 (− 1.89, 1.81) 0.97 0.60 (− 0.98, 2.19) 0.45 0.61 (− 1.20, 2.43) 0.51
EAA Horvath units: years
Unadjusted Intent to Treat 0.96 (− 0.76, 2.68) 0.27 − 0.20 (− 1.93, 1.52) 0.81 − 0.25 (− 1.97, 1.48) 0.78
Adjusted Intent to Treat 0.74 (− 1.06, 2.53) 0.42 − 0.34 (− 2.11, 1.43) 0.70 − 0.59 (− 2.43, 1.25) 0.53
Unadjusted High Adherence* − 0.26 (− 2.48, 1.97) 0.82 − 0.21 (− 2.15, 1.72) 0.83 0.38 (− 1.78, 2.55) 0.73
Adjusted High Adherence* − 0.11 (− 2.49, 2.26) 0.93 − 0.26 (− 2.28, 1.77) 0.80 0.04 (− 2.29, 2.37) 0.97
EAA SkinBloodClock units: years
Unadjusted Intent to Treat 0.81 (− 0.54, 2.15) 0.24 − 0.68 (− 2.03, 0.66) 0.32 0.26 (− 1.08, 1.61) 0.70
Adjusted Intent to Treat 0.86 (− 0.48, 2.19) 0.21 − 0.69 (− 2.01, 0.63) 0.30 0.40 (− 0.96, 1.77) 0.56
Unadjusted High Adherence* 1.01 (− 0.67, 2.68) 0.24 − 0.99 (− 2.45, 0.46) 0.18 0.52 (− 1.10, 2.15) 0.53
Adjusted High Adherence* 0.77 (− 0.90, 2.43) 0.37 − 1.09 (− 2.52, 0.34) 0.13 0.52 (− 1.12, 2.16) 0.53
Intrinsic EAA (IEAA) units: years
Unadjusted Intent to Treat 0.74 (− 0.96, 2.44) 0.39 − 0.22 (− 1.91, 1.48) 0.80 − 0.36 (− 2.06, 1.34) 0.68
Adjusted Intent to Treat 0.74 (− 1.05, 2.53) 0.42 − 0.40 (− 2.17, 1.37) 0.66 − 0.63 (− 2.47, 1.20) 0.50
Unadjusted High Adherence* − 0.38 (− 2.58, 1.82) 0.73 − 0.16 (− 2.08, 1.75) 0.87 0.12 (− 2.02, 2.26) 0.91
Adjusted High Adherence* − 0.06 (− 2.45, 2.32) 0.96 − 0.33 (− 2.36, 1.70) 0.75 0.02 (− 2.32, 2.35) 0.99
Extrinsic EAA (EEAA) units: years
Unadjusted Intent to Treat 1.39 (− 0.66, 3.44) 0.18 0.13 (− 1.92, 2.19) 0.90 1.56 (− 0.49, 3.62) 0.13
Adjusted Intent to Treat 1.05 (− 0.55, 2.66) 0.20 0.60 (− 0.99, 2.18) 0.46 0.56 (− 1.08, 2.20) 0.50
Unadjusted High Adherence* 1.57 (− 0.94, 4.08) 0.22 0.42 (− 1.77, 2.60) 0.71 1.79 (− 0.66, 4.23) 0.15
Adjusted High Adherence* − 0.12 (− 2.15, 1.90) 0.90 0.78 (− 0.95, 2.51) 0.38 0.70 (− 1.29, 2.68) 0.49
EAA PhenoAge units: years
Unadjusted Intent to Treat 1.92 (− 0.30, 4.14) 0.09 0.79 (− 1.43, 3.01) 0.48 0.40 (− 1.82, 2.63) 0.72
Adjusted Intent to Treat 2.02 (0.02, 4.03) 0.05 0.82 (− 1.16, 2.80) 0.41 − 0.12 (− 2.17, 1.93) 0.91
Unadjusted High Adherence* 3.32 (0.56, 6.08) 0.02 1.03 (− 1.37, 3.43) 0.40 0.58 (− 2.11, 3.27) 0.67
Adjusted High Adherence* 2.75 (0.18, 5.32) 0.04 0.98 (− 1.22, 3.17) 0.38 0.48 (− 2.04, 3.00) 0.70
EAA GrimAge units: years
Unadjusted Intent to Treat 0.76 (− 0.61, 2.12) 0.28 − 0.89 (− 2.26, 0.48) 0.20 0.26 (− 1.10, 1.63) 0.70
Adjusted Intent to Treat 0.76 (− 0.58, 2.10) 0.27 − 0.91 (− 2.24, 0.41) 0.18 − 0.39 (− 1.76, 0.98) 0.58
Unadjusted High Adherence* 1.61 (− 0.10, 3.33) 0.07 − 0.65 (− 2.14, 0.85) 0.39 0.45 (− 1.22, 2.12) 0.59
Adjusted High Adherence* 1.38 (− 0.33, 3.10) 0.11 − 0.74 (− 2.21, 0.73) 0.32 − 0.05 (− 1.73, 1.63) 0.95
DNAm TL Age Adjusted units: kb
Unadjusted Intent to Treat − 0.07 (− 0.14, 0.01) 0.09 − 0.03 (− 0.10, 0.05) 0.52 − 0.02 (− 0.09, 0.06) 0.67
Adjusted Intent to Treat − 0.04 (− 0.11, 0.02) 0.20 − 0.03 (− 0.10, 0.04) 0.41 0.01 (− 0.06, 0.08) 0.68
Unadjusted High Adherence* − 0.10 (− 0.20, − 9.5e−4) 0.05 − 2.2e−4 (− 0.09, 0.08) 0.99 − 0.03 (− 0.13, 0.07) 0.53
Adjusted High Adherence* − 0.06 (− 0.14, 0.03) 0.21 − 0.01 (− 0.08, 0.07) 0.80 0.01 (− 0.08, 0.09) 0.86
EpiTOC IR units: DNAm
Unadjusted Intent to Treat 5.7e−5 (− 5.9e−5, 1.7e−4) 0.34 5.7e−5 (− 5.9e−5, 1.7e−4) 0.34 1.1e−4 (− 5.0e−6, 2.3e−4) 0.06
Adjusted Intent to Treat 1.8e−5 (− 8.1e−5, 1.2e−4) 0.72 4.1e−5 (− 5.6e−5, 1.4e−4) 0.40 5.5e−5 (− 4.5e−5, 1.6e−4) 0.28
Unadjusted High Adherence* 3.0e−5 (− 1.2e−4, 1.8e−4) 0.69 8.9e−5 (− 3.8e−5, 2.2e−4) 0.17 9.0e−5 (− 5.2e−5, 2.3e−4) 0.21
Adjusted High Adherence* 6.6e−6 (− 1.17e−4, 1.3e−4) 0.92 8.5e−5 (− 2.1e−5, 1.9e−4) 0.12 5.1e−7 (− 1.2e−4, 1.2e−4) 0.99
EpiTOC2 IR units: cell divisions
Unadjusted Intent to Treat 3.78 (− 2.29, 9.85) 0.22 2.66 (− 3.41, 8.73) 0.39 5.91 (− 0.16, 11.98) 0.06
Adjusted Intent to Treat 1.43 (− 3.57, 6.44) 0.57 1.85 (− 3.10, 6.81) 0.46 2.73 (− 2.37, 7.84) 0.29
Unadjusted High Adherence* 2.79 (− 4.84, 10.42) 0.47 4.17 (− 2.47, 10.80) 0.22 4.82 (− 2.60, 12.24) 0.20
Adjusted High Adherence* 0.90 (− 5.46, 7.26) 0.78 4.07 (− 1.39, 9.53) 0.14 − 0.18 (− 6.41, 6.05) 0.95
MiAge IR units: cell divisions
Unadjusted Intent to Treat 0.28 (− 0.92, 1.45) 0.66 0.28 (− 0.90, 1.47) 0.64 0.69 (− 0.49, 1.88) 0.25
Adjusted Intent to Treat − 0.14 (− 1.05, 0.77) 0.77 0.13 (− 0.77, 1.03) 0.78 0.37 (− 0.56, 1.30) 0.44
Unadjusted High Adherence* 0.24 (− 1.22, 1.70) 0.75 0.46 (− 0.81, 1.73) 0.47 0.67 (− 0.75, 2.09) 0.35
Adjusted High Adherence* − 0.11 (− 1.26, 1.04) 0.85 0.49 (− 0.50, 1.48) 0.33 − 0.11 (− 1.24, 1.02) 0.85
  1. Adjusted models include adjustments for number of days from randomization to end of study and leukocyte abundance/proportions
  2. *Sample sizes for high adherence models are: placebo (N = 48), weight loss only (N = 23), metformin only (N = 36), and weight loss plus metformin (N = 25)
  3. EAA = epigenetic age acceleration (residuals of regressing epigenetic age on chronological age)
  4. IR = intrinsic rate of cell divisions (calculated by dividing mitotic clock measurements by chronological age)
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Clinical Epigenetics

ISSN: 1868-7083

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