Table 1.
Recent preclinical studies of sex differences in dietary restriction responses (2015–2017) in rodents.
| Type of dietary restriction | Preclinical model | Sexes included | Effect of sex | Reference |
|---|---|---|---|---|
| 30% CR (2 months) | C57BL/6 mice | M and F | The effect of CR on expression of some circadian clock genes, and IGF-1 signaling, was sex dependent | [25••] |
| 30% CR (lifelong) | C57BL/6 mice | M and F | CR resulted in an increase in lifespans in both males and females | [22•] |
| 20 and 40% CR (lifelong) | C57BL/6 and DBA/2J mice | M and F | 20% CR increased lifespan in both strains and sexes. 40% CR increased lifespan in C57BL/6 and DBA/2J males, but C57BL/6 females had no increased lifespan and DBA/2J females had no increase above that seen with 20% CR. | [21••] |
| 30% CR (lifelong) | Ercc1 Δ/− mice on C57BL/6 background | M and F | CR increased median lifespan 2-fold in females and 2.5-fold in males | [23] |
| 40% CR (lifelong) | Sprague Dawley Rats | M and F | Vitamin K concentrations decreased in both sexes with CR. PT was decreased in male CR rats, but not females | [26] |
| 40% CR (lifelong) | C57BL/6 and DBA/2J mice | M and F | CR reduced frailty index scores in C57BL/6 males, but not females. No significant effect of CR on frailty in DBA/2J mice | [27] |
| 3mo of a MetR diet in young (2mo) and old (9mo) mice | C57BL/6 mice | M and F | Males gain more weight compared to females that is attenuated with MetR; bone morphology is altered in an age-specific and sex-specific manner potentially under hormonal regulation. No impairment of bone biomechanical properties | [37•] |
| 10mo old mice fed MetR for 8 weeks | C57BL/6J mice | M and F | Sex independent improvement of glucose tolerance, and lower fasting blood glucose levels with MetR diet. Sex specific regulation of metabolic pathways with MetR: upregulation of FGF21 mRNA in MetR-fed females, while SIRT1 mRNA was upregulated in males | [35] |
| 14 week old mice fed a methionine deficient diet for 1 week | C57BL/6J mice | M and F | Sex independent energy expenditure in MetR mice; but a sex difference in the FGF21-UPC-1 axis, which is upregulated in males, but not females | [38] |
| TRF of a high fat diet | C57BL/6J mice | F only | Improvements in metabolic health in model of postmenopausal obesity | [43] |
| 4–5 week old mice on TRF for up to 26 days | C57BL/6NCrl mice | M only | TRF shifts the phase and alters the amplitude of the skin circadian clock, also altering ~10% of the skin transcription. They show that daytime-restricted feeding affects the sensitivity to DNA damage in the skin of mice, and dampens the expression of a key DNA repair factor, Xpa. The authors should consider replicating this study using both sexes and adult mice (16 weeks age) | [42] |
| 8 week old mice subjected to TRF at night | ICR mice | M and F | No difference in caloric intake, body weight, and locomotor activity rhythm in these young mice. The authors report that immobility in the forced swim test was higher in TRF male mice, but do not show convincing evidence to support this claim | [44] |
| 4 week old mice on IF (every other day feeding) for 9mo | C57BL/6J mice | M and F | Sex specific effects of IF on bodyweight (% bodyweight gain in males is more than females); decreased area and lower levels of heterogeneity in hepatocytes of IF animals that was sex independent; significant decreases in the expression of mRNA for caspase 3 and Bax in females but not males; this suggests IF promotes cellular maintenance in the liver which is more pronounced in females | [41] |
| EOD initiated in 5mo mice for 5 months | APP/PS1 double-transgenic mice [B6C3-Tg(APPswe, PS1dE) 85Dbo/J] and WT littermates | M and F | EOD feeding was protective in mice by protecting against Aβ deposition in the brains of AD mice and ameliorating some of the learning deficits. Sex was not considered as an independent variable by the authors when they performed their analysis of effects | [48] |
| 8–12 weeks old mice on IF for up to 40 days | C57BL/6J mice | F only | IF is protective when initiated in the early phases of autoimmune encephalitis but no mention of a sex specific effect | [47] |
CR, calorie restriction; MetR, methionine restriction; IGF-1, insulin-like growth factor 1; PT, prothrombin time; FGF21, fibroblast growth factor 21; M, male; F, female; AD, Alzheimer’s disease; WT, wild type; EOD, every other day; IF, intermittent fasting.