·       Diets low in specific protein components (branch-chain amino acids leucine, isoleucine, and valine) extend premature aging mouse lifespan.

·       Lifelong low branch-chain amino acid diets significantly increase the lifespan of healthy male mice but not female.

Dietary protein restrictions promote longevity in experimental animal species like mice and fruit flies. The protein components of restricted diets that mediate beneficial longevity effects haven’t been identified, but human data suggests elevated blood levels of specific protein components — branch-chain amino acids (BCAAs) leucine, isoleucine, and valine — are linked to an increased risk of age-related diseases.

Lamming and colleagues from the University of Wisconsin-Madison published a study in Nature Aging that indicated BCAA dietary restrictions increased mouse health and longevity with sex-specific benefits. They found lifelong BCAA dietary restriction extended the lifespan of males and improved the metabolism of both sexes. Their results demonstrate that diets with specific protein components can modulate health and lifespan. These dietary restrictions may translate to humans to facilitate longer and healthier lives.

Restricted Protein Diet Improves Lifespan and Survival in Prematurely Aging Mice

The research team from the University of Wisconsin-Madison assessed the effects of BCAA restriction on two mouse strains that exhibit premature aging called progeroid mice. In one of the strains, which was missing a protein called Lmna that is crucial to the intricate protein mesh network that provides nuclear structure (Lmna-/-), a low BCAA diet increased survival only in females. In the other strain, which carried a mutation that is found in most human cases of premature aging disease Hutchinson-Gilford Progeria Syndrome in the same Lmna gene (LmnaG609G/G096G), BCAA dietary restrictions significantly increased overall survival and maximum lifespan in both sexes. These results suggested BCAA restriction somehow protects against aging.

(Richardson et al., 2020 | Nature Aging) Lifelong BCAA diet-fed male and female premature aging mice exhibit significantly extended lifespan. Mice were fed low BCAA and low general amino acid protein component diets. The improved lifespans from these diets were significant in both cases yet were greatest with low BCAA diets.

Lifelong Dietary Protein Restriction Improves Metabolic Health

The team of researchers went on to test whether BCAA restricted diets induced these anti-aging effects. To do so, they followed a cohort of aged mice fed low branched-chain amino acid diets beginning at 16 months. Their assessments of metabolism indicated that the low branched-chain amino acid diets produced leaner mice with higher glucose tolerance — an indicator of metabolic health.

(Richardson et al., 2020 | Nature Aging) Low BCAA diets improve mouse metabolic health. The upper left graph illustrates low BCAA diet-fed mice weighed less starting around 19 weeks of age, a trend that continued to approximately 25 months. The upper right graph shows that a low BCAA diet significantly reduced mouse fat mass – an indicator of body fat weight. The lower graph shows reduced blood sugar (glucose), indicating improved glucose tolerance and metabolic health, after three weeks of low BCAA diet feeding.

A Lifelong Low Branch-Chain Amino Acid Diet Extends Male Mouse Lifespan

Since previous studies have shown dietary interventions provide more pronounced anti-aging effects when started in early life, Lamming and colleagues tested lifelong BCAA-restricted diets in unmodified, normal — wild-type — mice. Results indicated that while significant female lifespan extension did not occur, low BCAA-fed males had significantly improved lifespans with a 34.9% increase in median lifespan and an 18.2% increase in maximum lifespan. The longest-lived BCAA dietary-restricted male lived nearly 4 years (1,456 days), exceeding the lifespans of the longest living survivors in several previous studies by about 25%.

(Richardson et al., 2020 | Nature Aging) Lifelong BCAA dietary restriction significantly extends male but not female mouse lifespan. The left graph indicates females had no significant low BCAA diet-induced changes to lifespan. The right graph illustrates that males had a 34.9% increase in lifespan and an 18.2% maximal lifespan increase with low BCAA diets.

Future Studies May Show Whether Branch-Chain Amino Acid Restriction Provides Anti-Aging Effects in Humans

“Our results demonstrate that dietary levels of BCAAs are critically important in healthy aging, and provide new evidence that protein quality—the specific AA composition of dietary protein—is as important as the amount of dietary protein consumed,” concluded the authors. “Finally, while additional research and clinical trials will be required to determine how our findings apply to humans, our results support an emerging model that suggests that limiting dietary levels of BCAAs may be a key to a long and healthy life.” Future studies will need to identify how these results apply to humans, but this emerging model suggests BCAA dietary restriction may be key to a long and healthy life.

Foods high in BCAAs include whey, milk, and soy proteins, corn, beef, chicken, fish, and eggs. Tree nuts like almonds and cashews also have high BCAA content. Cutting these foods from one’s daily intake may allow a person to to try a low BCAA diet.