Aging and epigenetics: Longitudinal changes in gene-specific DNA methylation

Figures & data

Table 1. Baseline Characteristics of Participants in the Normative Aging Study, Boston, MA, 1999 - 2009 [mean (SD) or n (%)]

	Baseline Visit
	(n = 784)
Age (years)	72.3 (6.8)
Body mass index (kg/m^2)	28.2 (4.1)
Systolic blood pressure (mmHg)	132.6 (16.9)
Diastolic blood pressure (mmHg)	77.8 (9.3)
Fasting blood glucose (mg/dL)	108.6 (28.0)
Treatment with statins	280 (35.7)
Smoking status
Never	222 (28.3)
Former	530 (67.6)
Current	32 (4.1)
Cumulative smoking, pack-years^a	30.7 (27.3)
Season of clinical exam
Spring	192 (24.5)
Summer	218 (27.8)
Fall	241 (30.7)
Winter	133 (17.0)
Day of week of clinical exam
Monday	69 (8.8)
Tuesday	179 (22.8)
Wednesday	342 (43.6)
Thursday	194 (24.7)

^a Among current or former smokers

Table 2. Descriptive Statistics of Gene-specific Methylation by Visit for Participants in the Normative Aging Study, Boston, MA, 1999 - 2009

			Correlation (visit 1 and 2)		Methylation, % of 5-methyl cytosine
Gene	Visit Number	n	rho	P	Minimum	Maximum	Mean	Standard Deviation
GCR	1	735	0.116	0.0118	14.7	72.8	46.8	6.0
	2	471			22.3	87.2	47.2	6.4
	3	230			28.1	59.9	45.6	5.5
	4	29			28.8	54.1	45.1	5.4
	5	1			45.4	45.4	45.4	NA
iNOS	1	661	0.372	< 0.0001	24.5	87.2	69.4	7.3
	2	356			44.0	86.5	67.7	7.2
	3	148			37.8	79.4	65.7	7.8
	4	11			55.8	67.8	62.6	3.9
ICAM	1	707	0.557	< 0.0001	1.7	16.1	4.4	1.8
	2	428			1.6	12.0	4.1	1.8
	3	180			2.2	8.5	4.4	1.1
	4	24			2.5	5.9	3.5	0.7
	5	1			6.0	6.0	6.0	NA
IL6	1	780	0.705	< 0.0001	10.3	86.6	43.7	10.7
	2	547			12.3	81.3	42.8	9.9
	3	303			10.9	72.8	43.0	10.9
	4	45			18.3	66.2	43.6	11.1
	5	1			44.0	44.4	44.3	NA
TLR2	1	722	0.259	< 0.0001	0.0	8.9	3.1	1.3
	2	426			0.0	7.5	3.0	1.3
	3	166			0.0	7.2	2.7	1.2
	4	26			0.9	5.1	2.0	1.1
IFNγ	1	784	0.467	< 0.0001	30.9	95.7	84.4	5.5
	2	541			51.6	94.4	85.1	5.0
	3	295			59.0	95.0	85.3	4.6
	4	42			77.1	94.6	86.6	3.6
	5	1			80.1	80.1	80.1	NA
F3	1	759	0.210	< 0.0001	0.0	14.8	2.3	1.3
	2	478			0.0	11.1	2.6	1.3
	3	191			0.0	6.9	2.6	1.2
	4	27			0.6	3.7	1.7	0.7
CRAT	1	770	0.487	< 0.0001	1.0	7.4	3.2	1.0
	2	519			1.2	7.0	3.1	1.2
	3	268			1.5	6.2	3.3	0.9
	4	37			1.6	5.9	3.1	0.9
OGG	1	633	0.171	0.0024	0.0	11.8	2.2	1.4
	2	314			0.0	7.7	2.2	1.3
	3	100			0.0	7.8	2.6	1.6
	4	6			1.4	4.8	3.2	1.1

Table 3. Association Between Gene-specific Methylation and Age at Visit in the Normative Aging Study, Boston, MA, 1999 - 2009

	Unadjusted		Adjusted ^b
Gene	Change in % 5mC ^a	95% CI	Change in % 5mC ^a	95% CI
GCR	-0.042	-0.090, 0.006	-0.044	-0.099, 0.011
iNOS	-0.164	-0.230, -0.097*	-0.154	-0.229, -0.079*
ICAM	-0.016	-0.031, -0.001*	-0.010	-0.028, 0.007
IL6	-0.033	-0.113, 0.047	0.000	-0.096, 0.095
TLR2	0.005	-0.006, 0.016	0.015	0.002, 0.027*
IFNγ	0.017	-0.024, 0.058	-0.019	-0.062, 0.024
F3	0.004	-0.006, 0.014	-0.001	-0.013, 0.010
CRAT	0.010	0.001, 0.018	0.008	-0.001, 0.018
OGG	0.006	-0.007, 0.019	0.004	-0.011, 0.019

% 5mC: % 5-methyl-cytosine * p < 0.05 ^a Change in % 5mC associated with a 1-y increase in age at visit ^b Adjusting for BMI, SBP, DBP, fasting blood glucose, % lymphocytes, % neutrophils, use of statin, season, day of week, smoking status, and pack-years

Table 4. Association Between Gene-specific Methylation and Cross-sectional Age and Change in Age Over Time in the Normative Aging Study, Boston, MA, 1999 - 2009

		Unadjusted		Adjusted ^b
				Full Cohort		No IHD at Baseline
Gene		Change in % 5mC ^a	95% CI	Change in % 5mC ^a	95% CI	Change in % 5mC ^a	95% CI
GCR	Cross-sectional age	-0.022	-0.073, 0.029	-0.031	-0.087, 0.025	-0.038	-0.104, 0.028
	Longitudinal age	-0.151	-0.256, -0.046*	-0.191	-0.321, -0.061*	-0.212	-0.365, -0.059*
iNOS	Cross-sectional age	-0.063	-0.133, 0.007	-0.097	-0.173, -0.022*	-0.120	-0.212, -0.028*
	Longitudinal age	-0.660	-0.795, -0.526*	-0.695	-0.860, -0.531*	-0.661	-0.860, -0.462*
ICAM	Cross-sectional age	-0.012	-0.029, 0.004	-0.010	-0.028, 0.008	-0.007	-0.028, 0.015
	Longitudinal age	-0.030	-0.059, -0.002*	-0.015	-0.051, 0.021	0.003	-0.041, 0.047
IL6	Cross-sectional age	0.001	-0.101, 0.103	0.025	-0.083, 0.133	-0.002	-0.125, 0.122
	Longitudinal age	-0.081	-0.198, 0.037	-0.064	-0.221, 0.094	-0.097	-0.277, 0.082
TLR2	Cross-sectional age	0.016	0.004, 0.028*	0.020	0.007, 0.032*	0.015	-0.001, 0.030
	Longitudinal age	-0.054	-0.078, -0.031*	-0.033	-0.062, -0.004*	-0.025	-0.060, 0.011
IFNγ	Cross-sectional age	-0.033	-0.080, 0.014	-0.040	-0.084, 0.005	-0.031	-0.081, 0.020
	Longitudinal age	0.154	0.081, 0.227*	0.110	0.021, 0.198*	0.130	0.032, 0.229*
F3	Cross-sectional age	-0.002	-0.013, 0.008	-0.005	-0.017, 0.006	-0.001	-0.015, 0.012
	Longitudinal age	0.040	0.017, 0.062*	0.041	0.014, 0.068*	0.055	0.023, 0.086*
CRAT	Cross-sectional age	0.006	-0.003, 0.015)	0.005	-0.005, 0.015	0.006	-0.006, 0.018
	Longitudinal age	0.023	0.006, 0.039*	0.036	0.015, 0.057*	0.033	0.009, 0.058*
OGG	Cross-sectional age	-0.006	-0.019, 0.007	-0.002	-0.016, 0.013	-0.004	-0.022, 0.015
	Longitudinal age	0.084	0.055, 0.113*	0.081	0.045, 0.116*	0.088	0.045, 0.130*

% 5mC: % 5-methyl-cytosine; IHD: Ischemic Heart Disease * p < 0.05 ^a Change in % 5mC associated with a 1-y increase in cross-sectional age or longitudinal age ^b Adjusting for BMI, SBP, DBP, fasting blood glucose, % lymphocytes, % neutrophils use of statin, season, day of week, smoking status, and pack-years

Figure 1. Plots of Subject-specific Slopes for Change in Age in the Normative Aging Study, Boston, MA, 1999 – 2009.