Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis

Abstract

Biological aging measures have been proposed as proxies for extension of healthy life span in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans.

Keywords: Biological age; Caloric restriction; Geroprotector; Geroscience.

© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

CALERIE participants’ KDM Biological Ages were highly correlated with their chronological ages at the time of baseline assessment but tended to be slightly younger. The plotted line shows a one-to-one correspondence between biological age and chronological age. The larger number of plotted points below the line as compared to above the line indicates that CALERIE participants’ KDM Biological Ages tended to be slightly younger than their chronological ages.

Figure 2.

Change in KDM Biological Age from Baseline to 12- and 24-month follow-ups in the ad libitum (black dots) and caloric-restriction (blue dots) arms of the CALERIE trial. Panel A shows mean values with 95% confidence intervals calculated for each follow-up. Panel B shows slopes estimated from the growth model with the shaded areas indicating 95% confidence intervals.