Dietary interventions such as caloric restriction (CR) have been shown to prolong lifespan in multiple species, but adherence to a CR diet is difficult, so it is critical to develop eating patterns that mimic the benefits of the CR diet without reducing energy intake.
Previous studies have shown that protein restriction (PR), especially isoleucine restriction (ILER), can improve multiple markers of metabolic health, reduce obesity, and improve insulin sensitivity. However, the mechanisms that mediate these beneficial effects are currently unknown.
Recently, Dudley W. from the University of Wisconsin-MadisonProf. Lamming's group published an article entitled "Dietary Restriction of Isoleucine Increases Healthspan and Lifespan of Genetically Heterogeneous Mice" in the journal Cell Metabolism.
The article found that ILER can improve metabolic health, promote ** and glycemic control and ultimately extend the lifespan and healthy life of mice in both young and old mice.
The researchers first divided 9-week-old male and female HET3 mice into three groups on a normal amino acid diet, a low amino acid diet, and a low isoleucine diet, all of which were equal in calories. It was found that both male and female mice in both the normal diet group and the low amino acid diet group increased their body weight, while the male and female mice in the low isoleucine diet group initially decreased their body weight, but the female mice gradually regained their weight.
After 3 weeks, the researchers tested the mice for glucose tolerance and found that mice fed with low isoleucine showed improved glucose tolerance. Overall, these results suggest that a low-isoleucine diet was able to reduce body weight and improve glycemic control in mice, and was more effective at promoting metabolic health than the low-amino acid diet group.
The researchers then used the recently developed Mouse Frailty Index to study the effects of diet, age, and sex on frailty. As expected, the degree of frailty increased with age in male and female mice on a normal amino acid diet, and the frailty index was significantly reduced in male mice fed with low amino acids and low isoleucine at multiple time points.
Consistent with the frailty index, a low-isoleucine diet significantly increased male mouse lifespan from 6 months of age, with a median lifespan of 33% relative to control mice. Surprisingly, although a low-amino acid diet reduced weakness, it had no effect on male lifespan.
In conclusion, the study demonstrated that isoleucine restriction in mice from 6 months of age (roughly equivalent to the human in their 30s) can prolong healthy lifespans and longevity. This benefit has been observed in both sexes, and this effect is particularly pronounced in males.
The fact that ILER plays a role in genetically heterogeneous populations suggests that this intervention may be well applicable in humans. More importantly, ILER improves metabolic health, but does not induce CR ** "binge-eating" behavior and prolongs the median lifespan of females.
Reference: This article was originally published on December 27, 2023 in "aging".