Male and female C57BL/6J.Nia mice were placed on Control AA and Low His diets starting at 16 months of age. (A-D) Fat mass and lean mass were determined at multiple time points (n= n varies by month; maximum n = 9 Ctrl AA females, 10 Low His females, 14 Ctrl AA males, 10 Low His males). (E) Frailty was assessed at 19 and 24 months of age. (A-E) Statistics for the overall effects of diet, age and the interaction represent the P value from a mixed-effects model (restricted maximum likelihood (REML)), *p<0.05, two-sided Sidak’s post hoc test. (F-G) Glucose tolerance was determined in (F) 23 month old females and (G) 25 month old males (n = 7–13/group females and 10–11/group males, *p < 0.05, t-test). (H-I) Kaplan–Meier plots showing the survival of female (H) and male (I) C57BL/6J.Nia mice fed the indicated diets starting at 16 months of age.