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Isoleucine, like other branched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.{{pmid|25287287}} In diet-induced obese and insulin resistant mice, a diet with decreased levels of isoleucine (with or without the other branched-chain amino acids) results in reduced adiposity and improved insulin sensitivity.{{pmid|29266268}}{{pmid|33887198}} Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet.{{pmid|33887198}} In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.{{pmid|27346343}} In humans, higher dietary levels of isoleucine are associated with greater body mass index.{{pmid|33887198}}
Isoleucine, like other branched-chain amino acids, is associated with insulin resistance: higher levels of isoleucine are observed in the blood of diabetic mice, rats, and humans.{{pmid|25287287}} In diet-induced obese and insulin resistant mice, a diet with decreased levels of isoleucine (with or without the other branched-chain amino acids) results in reduced adiposity and improved insulin sensitivity.{{pmid|29266268}}{{pmid|33887198}} Reduced dietary levels of isoleucine are required for the beneficial metabolic effects of a low protein diet.{{pmid|33887198}} In humans, a protein restricted diet lowers blood levels of isoleucine and decreases fasting blood glucose levels.{{pmid|27346343}} In humans, higher dietary levels of isoleucine are associated with greater body mass index.{{pmid|33887198}}


[[File:isoleucine Restriction in UM-HET3 mice.jpg|thumb|Isoleucine restriction in UM-HET3 mice<br>(Low ILE = Low isoleucine, Low AA = Low amino acid)]]
=== Isoleucine Restriction ===
=== Isoleucine Restriction ===
Isoleucine restriction (IleR) has been identified as a significant factor in improving metabolic health and extending lifespan, particularly in genetically heterogeneous UM-HET3 mice. Restricting dietary isoleucine promotes leanness and glycemic control in both sexes, while also reprogramming hepatic metabolism in a sex-specific manner. Notably, IleR has been observed to reduce frailty and increase the lifespan by 33% of both male and female mice, with more pronounced effects in males. These findings suggest that IleR, or pharmaceuticals that mimic its effects, might serve as a geroprotective intervention, offering potential benefits for healthspan and longevity. The research underscores the importance of isoleucine in diet and aging, and its potential as a target for nutritional and pharmacological interventions in the field of gerontology.{{pmid|37939658}}
Recent research has revealed that dietary isoleucine restriction (IleR) by 67% can have significant effects on metabolic health and lifespan, particularly in genetically heterogeneous UM-HET3 mice. Implemented in 9-week-old mice, IleR has been shown to promote leanness and improve glycemic control across genders. Additionally, it has been noted to cause sex-specific reprogramming of hepatic metabolism.{{pmid|37939658}}<ref>https://www.lifespan.io/news/isoleucine-restriction-boosts-lifespan-in-mice/</ref>
 
In male mice, a 33% increase in median lifespan was observed, along with a notable increase in maximum lifespan when compared to control groups. These findings are some of the most significant among interventions tested in rodent models. For female mice, the increase in maximum lifespan was more modest, at 7%. Correspondingly, male mice under IleR also experienced significantly reduced levels of frailty compared to their counterparts. The study also addresses mortality causes, indicating that while cancer accounts for the majority of deaths in HET3 mice, male mice on an IleR diet were considerably less likely to develop cancer, a benefit not as evident in female mice.
 
These findings suggest that isoleucine restriction, or pharmacological agents that replicate its effects, may offer a promising [[Geroprotection|geroprotective]] strategy, potentially enhancing healthspan and longevity. Such findings underscore the significant role of isoleucine in diet and aging and point to its viability as a target for both nutritional and pharmacological interventions in gerontology.


== See Also ==
== See Also ==
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* {{pmid text|37939658}}


== References ==
== References ==
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[[Category:Lifespan Reducing]]
[[Category:Lifespan Reducing]]
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