Dietary restriction in rats and mice: A meta-analysis and review of the evidence for genotype-dependent effects on lifespan

Abstract

Laboratory survival experiments have shown that dietary restriction (DR) can increase median and maximum lifespan. This paper provides a meta-analysis of laboratory experiments that have evaluated the effects of DR on lifespan in rats and mice (1934 – present). In rats, DR increased median lifespan by 14 – 45% in half of all experiments, but in mice the effects of DR have been much weaker (4 – 27%). The least favorable effects of DR on lifespan have been observed among inbred rather than non-inbred mouse strains. In fact, some inbred mouse strains do not necessarily live longer with DR, including DBA/2 male mice and several strains from the ILSXISS recombinant inbred panel. Shortening of lifespan with DR has also been observed and confirmed for ILSXISS strain 114. Importantly, all rodent studies may be biased by the effects of laboratory breeding, since one study has shown that median lifespan is not improved by DR in wild-derived mice. These findings suggest that the set of genetic backgrounds studied in rodent DR experiments should be diversified. This will broaden the scope of genotypes studied in aging research, but may also be critical for translation of findings from rodents to historically outbred and genetically heterogeneous primate species.

The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice

“…All procedures were reviewed and approved by University of Aberdeen ethical approval committee and carried out under a Home Office issued licence compliant with the Animals (Scientific Procedures) Act 1986. This strain is already known to live longer under CR (Turturro et al ., 1999; Swindell, 2012). More information on procedures and measures can be found in Data S10 and the first paper of this series (Mitchell et al ., 2015c).…”

Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

“…Even though DR repeatedly induced lifespan prolongation in rodents, DR does not increase lifespan in all mouse strains [58]. In wild mice, DR even increased mortality in early life [59].…”

Dietary restriction and the pursuit of effective mimetics

“…The absence of significant lifespan effects in some studies may be due to small sample sizes, whereby single individuals have a large effect on the overall group survival (13,57) . Indeed, and as reviewed in detail elsewhere (8) , contemporary analysis of some of the early rat DR studies suggest that the lifespan extension effects reported may have been somewhat overestimated. Large sample sizes may also produce negligible but significant lifespan effects that might have little relevance to the actual biology (8) .…”

“…Indeed, and as reviewed in detail elsewhere (8) , contemporary analysis of some of the early rat DR studies suggest that the lifespan extension effects reported may have been somewhat overestimated. Large sample sizes may also produce negligible but significant lifespan effects that might have little relevance to the actual biology (8) . There are also some suggestions that DR may affect the ageing trajectory differently in mice and rats, and this may also be the case within different strains.…”