|IL'YASOVA, DORA - Georgia State University|
|FONTANA, LUIGI - Washington University|
|BHAPKAR, MANJUSHRI - Duke University|
|PIEPER, CARL - Duke University|
|SPASOJEVIC, IVAN - Duke University|
|REDMAN, LEANNE - Pennington Biomedical Research Center|
|DAS, SAI KRUPA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|HUFFMAN, KIM - Duke University|
|KRAUS, WILLIAM - Duke University|
Submitted to: Aging Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2017
Publication Date: 2/9/2018
Citation: Il'yasova, D., Fontana, L., Bhapkar, M., Pieper, C.F., Spasojevic, I., Redman, L.M., Das, S., Huffman, K.M., Kraus, W.E. 2018. Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: the CALERIE 2 randomized clinical trial. Aging Cell. 17(2):e12719. https://doi.org/10.1111/acel.12719.
Interpretive Summary: Nutrition plays a central role in modulating changes in metabolism and health with aging. In particular, caloric restriction (CR) has been suggested to not only slow aging but also lower the risk for multiple diseases based on research in numerous species, including mammals. One mechanism by which CR is thought to minimize the risk for chronic disease is by reducing oxidative stress, a process which causes damage and inflammation in multiple tissues. The National Institutes of Health-funded CALERIE trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) examined the effect of 2 year CR on oxidative stress in healthy non-obese participants randomly allocated to the CR group or to a control group that was on ad-libitum intake. A urinary marker of oxidative stress (F2-Isoprostanes) was measured at baseline, and at 1 and 2 years of CR. On average participants achieved 12% sustained CR over the two year period. In comparison to the control group the CR group had reductions in markers of oxidative stress by 17% at 1year and 13 % at 2 years of CR. A two-year CR intervention resulted in favorable changes in whole body oxidative stress.
Technical Abstract: Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2-isoprostanes were quantified using LC-MS/MS in morning, fasted urine specimens at baseline, at 12 and 24 months. The primary measure of oxidative status was creatinine-adjusted 2,3 dinor iPF(2a)-III concentration, additional measured included iPF(2a) III, iPF2a-VI, and 8,12-iso-iPF2a-VI. Intention-to-treat analyses assessed change in 2,3 dinor iPF(2a)-III using mixed models assessing treatment, time, and treatment-by-time interaction effects, adjusted for blocking variables and baseline F2-isoprostane value. Exploratory analyses examined changes in iPF(2a) III, iPF(2a)-VI, and 8,12 iso iPF(2a)-VI. A factor analysis used aggregate information on F2 isoprostane values. In CR group, 2,3-dinor iPF(2a) III concentrations were reduced from baseline by 17% and 13% at 12 and 24 months, respectively; these changes were significantly different from AL group (p < .01). CR reduced iPF(2a) III concentrations by 20% and 27% at 12 and 24 months, respectively (p < .05). The effects were weaker on the VI species. CR caused statistically significant reduction in isoprostane factor at both time points, and mean (se) changes were -0.36 (0.06) and -0.31 (0.06). No significant changes in isoprostane factor were at either time point in AL group (p < .01 between-group difference). We conclude that two-year CR intervention in healthy, non-obese men and women reduced whole body oxidative stress as assessed by urinary concentrations of F2 isoprostanes.