Epigenetic Aging Mediates the Association between Pain Impact and Brain Aging in Middle to Older Age Individuals with Knee Pain

Figures & data

Table 1. Participant characteristics with and without knee pain (n = 174).

	No pain (n = 26)	Low impact pain (n = 95)	High impact pain (n = 53)	P	Direction
Age	59.58 ± 9.33	58.63 ± 7.96	56.63 ± 7.12	0.052
Female	18 (69%)	62 (65%)	30 (56%)	0.650
Study location (UF)	17 (65%)	62 (65%)	30 (56%)	0.752
NHW*	17 (65%)	59 (62%)	21 (39%)	0.026	>NHB in HIP
Height (cm)	166.20 ± 7.65	168.04 ± 8.89	170.44 ± 9.37	0.161
Weight (kg) *	83.68 ± 16.51	85.16 ± 18.41	92.54 ± 18.67	0.009	HIP>CON
BMI (kg/m^2)	30.30 ± 5.71	30.32 ± 6.68	31.87 ± 6.04	0.074
Smoking History (Yes)	8 (30%)	35 (37%)	31 (59%)	0.013	HIP>LIP+CON
Pain Severity*	0.00 ± 0.00	11.83 ± 6.90	20.30 ± 5.39	<0.001	HIP>LIP>CON
Disability Score*	9.38 ± 1.96	5.95 ± 5.88	50.96 ± 46.23	<0.001	HIP>LIP+CON
DNAmGrimAge-diff*	0.09 ± 3.31	1.32 ± 5.41	5.14 ± 5.66	<0.001	HIP>LIP+CON
Brain-PAD*	−3.46 ± 7.49	−4.13 ± 7.63	−0.89 ± 6.24	0.020	HIP>LIP

*Denotes significant difference. NHW, non Hispanic white; NHB, non Hispanic black; BMI, body mass index; HIP, high impact pain; LIP, low impact pain; CON, control.

Figure 1. Relationship between DNAmGrimAge-difference and brain-PAD (green = no pain, yellow = low impact pain, red = high impact pain).

Note: *P < 0.05. IV, independent variable; DV, dependent variable; GCPS, Graded Chronic Pain Scale.

Figure 2. Mediation analysis of pain group, DNAmGrimAge-difference and brain-PAD. Bias corrected bootstrapped estimates and confidence intervals.

Table 2. Bias corrected bootstrapped estimates and confidence intervals for direct and mediated effects of pain severity and disability GCPS scores on brain-PAD adjusting for covariates.

	Pathway	Coefficient (CI)
GCPS Pain Severity	Direct effect (c)	0.022 (−0.022; 0.066)
	IV>Mediator (a)	0.149 (0.023; 0.070)*
	Mediator>DV (b)	0.297 (0.023; 0.570)*
	Mediation (a + b)	0.014 (0.002; 0.029)*
GCPS Disability	Direct effect (c’)	0.034 (−0.047; 0.073)
	IV>Mediator (a)	0.040 (0.019; 0.062)*
	Mediator>DV (b)	0.270 (0.001; 0.541)*
	Mediation (a + b)	0.011 (0.001; 0.023)*

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.