Table 4.

Targeted Profiling of Muscle Mitochondrial Function and the Oxidative Stress Response After 12 Months of Caloric Restriction

	Control Group (n = 8)		CR Group (n = 15)		P Value
	Baseline	Month 12	Baseline	Month 12	Group	Time	Group × Time
Muscle mitochondrial biogenesis and function
ACACB	1.50 ± 0.21	1.32 ± 0.15	1.21 ± 0.11	1.21 ± 0.07	0.22	0.39	0.39
ACSL1	0.635 ± 0.059	0.537 ± 0.056a	0.585 ± 0.052	0.557 ± 0.049	0.85	0.01	0.13
CD36	0.778 ± 0.047	0.680 ± 0.037	0.661 ± 0.076	0.594 ± 0.074	0.32	0.07	0.72
CPT1B	1.83 ± 0.14	1.48 ± 0.15	1.61 ± 0.16	1.98 ± 0.33	0.62	0.95	0.14
CS	0.528 ± 0.035	0.454 ± 0.030a	0.470 ± 0.038	0.448 ± 0.030	0.53	0.01	0.11
HADH	0.713 ± 0.051	0.634 ± 0.055	0.672 ± 0.067	0.599 ± 0.057	0.67	0.03	0.94
MLYCD	0.848 ± 0.097	0.652 ± 0.068	0.673 ± 0.072	0.686 ± 0.078	0.52	0.09	0.06
NAMPT	0.993 ± 0.078	0.854 ± 0.084	0.866 ± 0.061	1.370 ± 0.435	0.52	0.57	0.32
NRF1	0.581 ± 0.043	0.559 ± 0.040	0.537 ± 0.028	0.592 ± 0.038	0.91	0.50	0.11
PPARA	0.482 ± 0.043	0.429 ± 0.039	0.463 ± 0.041	0.420 ± 0.029	0.79	0.01	0.77
PPARD	2.48 ± 0.26	2.47 ± 0.44	2.06 ± 0.18	2.30 ± 0.26	0.31	0.71	0.67
PPARGC1A	10.79 ± 0.88	8.92 ± 1.27	9.19 ± 0.73	10.19 ± 1.09	0.89	0.63	0.12
PPARGC1B	0.651 ± 0.063	0.700 ± 0.079	0.648 ± 0.054	0.635 ± 0.048	0.64	0.71	0.52
PRKAA1	5.54 ± 0.73	5.46 ± 0.66	4.39 ± 0.26	5.87 ± 1.10	0.68	0.42	0.36
PRKAA2	0.537 ± 0.042	0.587 ± 0.042	0.544 ± 0.042	0.565 ± 0.035	0.90	0.11	0.50
PRKAG3	0.467 ± 0.036	0.473 ± 0.048	0.436 ± 0.038	0.413 ± 0.035	0.41	0.72	0.55
SCD	0.131 ± 0.030	0.225 ± 0.061	0.249 ± 0.054	0.227 ± 0.065	0.41	0.49	0.28
SIRT1	0.950 ± 0.120	0.786 ± 0.080	0.791 ± 0.135	0.919 ± 0.104	0.94	0.77	0.03
SLC25A4	0.715 ± 0.052	0.723 ± 0.070	0.745 ± 0.069	0.688 ± 0.074	0.97	0.74	0.66
UCP3	4.86 ± 0.34	3.89 ± 0.44	3.75 ± 0.33	3.99 ± 0.45	0.35	0.25	0.07
Muscle mitochondrial content
Complex III protein	0.172 ± 0.019	0.143 ± 0.010	0.174 ± 0.015	0.176 ± 0.014	0.39	0.27	0.27
Complex IV protein	0.0332 ± 0.006	0.0310 ± 0.005	0.0448 ± 0.003	0.0405 ± 0.006	0.05	0.56	0.84
mtDNA copy number	1800 ± 88	1580 ± 64	1935 ± 95	1535 ± 100a	0.76	<0.01	0.23
Muscle mitochondrial oxidative stress response
CPEB2	0.639 ± 0.031	0.612 ± 0.065	0.598 ± 0.036	0.560 ± 0.021	0.28	0.38	0.88
GPX1	1.66 ± 0.11	1.27 ± 0.17	1.51 ± 0.13	1.76 ± 0.36	0.55	0.81	0.26
GPX7	0.710 ± 0.050	0.704 ± 0.085	0.676 ± 0.033	0.648 ± 0.017	0.35	0.66	0.79
GSTK1	0.976 ± 0.045	0.831 ± 0.062	0.973 ± 0.055	0.865 ± 0.027	0.77	0.01	0.69
HMOX1	8.98 ± 0.69	6.77 ± 1.61	11.64 ± 1.78	17.54 ± 5.44	0.12	0.64	0.32
NQO1	0.0639 ± 0.007	0.0501 ± 0.006	0.0601 ± 0.005	0.0562 ± 0.005	0.89	0.01	0.15
OGG1	0.287 ± 0.020	0.261 ± 0.017	0.259 ± 0.018	0.277 ± 0.014	0.81	0.66	0.02
PPM1L	0.947 ± 0.097	0.803 ± 0.071	0.850 ± 0.091	0.778 ± 0.055	0.59	0.03	0.44
SOD2	0.561 ± 0.053	0.445 ± 0.049a	0.515 ± 0.049	0.473 ± 0.035	0.89	0.002	0.12
4-HNE protein adducts	2.55 ± 0.71	1.64 ± 0.30	2.19 ± 0.44	2.56 ± 0.67	0.68	0.58	0.23

Data are mean ± standard error of the mean for all participants. Only participants who complied with the intervention protocols and completed the intervention were included. Italics indicate mRNA expression. See Materials and Methods for details on the individual methods related to this table.

Abbreviations: ACACB, acetyl-CoA carboxylase β; ACSL1, acyl-CoA synthetase long-chain family member 1; CPEB2, cytoplasmic polyadenylation element binding protein 2; CPT1B, carnitine palmitoyltransferase 1B; CS, citrate synthase; GPX1, glutathione peroxidase 1; GPX7, glutathione peroxidase 7; GSTK1, glutathione S-transferase κ-1; HADH, hydroxyacyl-CoA dehydrogenase; HMOX1, heme oxygenase 1; MLYCD, malonyl-CoA decarboxylase; NAMPT, nicotinamide phosphoribosyltransferase; NQO1, NAD(P)H quinone dehydrogenase 1; NRF1, nuclear respiratory factor 1; OGG1, 8-oxoguanine DNA glycosylase; PPARA, peroxisome proliferator-activated receptor α; PPARD, peroxisome proliferator activated receptor δ; PPARGC1A, peroxisome proliferator-activated receptor, γ, coactivator 1 α; PPARGC1B, peroxisome proliferator-activated receptor, γ, coactivator 1 β; PPM1L, protein phosphatase, Mg²⁺/Mn²⁺ dependent 1L; PRKAA1, protein kinase AMP-activated catalytic subunit α 1; PRKAA2, protein kinase AMP-activated catalytic subunit α 2; PRKAG3, protein kinase AMP-activated catalytic subunit γ 3; qRT-PCR, quantitative reverse transcription polymerase chain reaction (Western blotting); SCD, stearoyl-CoA desaturase; SIRT1, sirtuin 1; SLC25A4, solute carrier family 25 member 4/adenine nucleotide transporter 1; SOD2, superoxide dismutase 2, mitochondrial; UCP3, uncoupling protein 3.

^aWithin group, significant difference from baseline to month 12.