FIGURE 1.

IMR of male mice produces similar healthspan benefits to continuous MR and prevents liver steatosis. Comparisons over time of average values for (a) total body mass, (b) food consumption, and (c) food consumption normalized to total body mass for control‐fed (CF; black circles) or continuously methionine‐restricted (MR; red squares) male mice, as well as animals subjected to IMR (IMR1; light blue triangles) or a more stringent IMR regimen (IMR2; dark blue triangles). For simplicity, food consumption graphs (b‐c) show values integrated over 7 days of feeding; expanded graphs are presented in Figure S2. Average values at conclusion of the experiment (~6 weeks) are also shown for (d) total body mass, (e) mass of inguinal fat pads, (f) mass of perigonadal fat pads, (g) liver mass, (h) lean body mass, and (i) body length. Representative photomicrographs (200× magnification) of the livers of mice fed either (j) the control diet or (k) the IMR2 regimen for ~16 weeks, as well as (l) a comparison of the mean steatosis grades of these animals. For panel D, the colored triangle denotes that weighing of the indicated group occurred following a period of MR. For panels a‐i and l, bars denote SEM. For panels j‐k, bars represent 100 µm. For panels d‐i and l, statistically significant differences (as compared with CF values) are indicated (*p < 0.05; **p < 0.01; ***p < 0.001). For panels d‐i, statistically significant differences between MR and IMR2 values are either indicated (*p < 0.05) or absent (ns). For panels a‐i, N = 4 for all groups; for panel l, N = 6 for both groups