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Acknowledgments

We are grateful to the study participants, investigators, and clinical support staff involved in the CALERIE study and D. K. Ingram and T. Horvath for presubmission review of this manuscript.

Funding: This research was supported in part by the National Institutes of Health (NIH grants AG031797, AG045712, P01AG051459, and AR070811 to V.D.D.); the Glenn Foundation for Medical Research (V.D.D.); Cure Alzheimer’s Fund (V.D.D.); and the Aging Biology Foundation (M.N.A.). The CALERIE study was funded by the National Institute on Aging (grants U01AG022132, U01AG020478, U01AG020487, and U01AG020480).

Author contributions: O.S. performed human adipose tissue and CD4 T cell RNA sequencing and all mouse experiments, analyzed data, and participated in manuscript preparation. I.S. analyzed RNA-sequencing data. Y.Y. performed experiments and data analyses for T cell TREC and the MRI study and supported the mouse phenotyping studies. S.R. performed qPCR experiments, analyzed data, and prepared the manuscript. S.S. and A.P. analyzed RNA-sequencing data. A.R. and K.N. analyzed the thymic MRI data. S.R.S. and E.R. designed the CALERIE study, were involved in experimental design and data analysis, and provided critical reviews. C.G. supervised the thymic MRI data acquisition, analysis, and interpretation. M.A. provided critical reviews and supervised the bioinformatic analyses and interpretation of the transcriptome data. All authors participated in manuscript preparation. V.D.D. conceived the project, helped with data analysis and interpretation, and wrote the manuscript;

Competing interests: The authors declare no competing interests.