There are numerous dietary approaches that can intervene in and alter the aging process—from the so-called "universally most powerful" caloric restriction to strategies like the Mediterranean diet and DASH diet.
Beyond these widely recognized anti-aging dietary patterns, some dietary measures have long been controversial—such as the protein and amino acid restriction diets we discuss today.
Most debates around protein and amino acid restriction stem from people’s traditional perception of protein: as an essential substance for life activities, it doesn’t cause weight gain even in excess; it helps children grow taller and keeps the elderly steady on their feet. However, for most ordinary young adults and middle-aged people with growing anti-aging needs, the truth about protein may be quite different.
1. Protein Restriction: Eat Less, Live Longer
As early as 2005, Professor Linda Partridge, a top scientist in the field of aging, discovered that caloric restriction cannot fully explain the anti-aging effects of dietary restriction. When nematodes in different groups consumed the same number of calories, differences in nutrient composition led to significant variations in lifespan extension[1].
Figure Notes:
- (A, B) Lifespan analysis of fruit flies under different nutrient compositions.
Subsequent studies on dietary anti-aging further highlighted the importance of nutrient composition. In 2014, Australian nutritionist Professor Stephen Simpson confirmed that the ratio of different nutrients is the decisive factor for an organism’s health and longevity—and special attention should be paid to protein intake[2].
In follow-up studies using various model organisms, scholars successively found that simply controlling the daily protein intake ratio (without affecting calorie intake) can extend the lifespan of yeast, fruit flies, and mice[2-4].
What’s more, protein restriction has also been proven to be closely related to human aging: middle-aged people who follow a low-protein diet have a lower risk of cardiovascular disease, cancer, and even significantly reduced mortality[5-7].
For example, an 18-year follow-up study of over 6,000 Americans aged 50 and above found that high-protein diets increased cancer mortality by 4 times and overall mortality by approximately 75% in middle-aged people (50-65 years old)[7].
The potential mechanism behind this benefit is thought to involve:
- Activating GCN2 (a serine/threonine kinase) and the transcription factor ATF4,
- Increasing the liver-derived factor FGF21 in the body,
- Downregulating the AKT-mTOR pathway[8, 9],
- Possibly regulating GHR (growth hormone receptor)-IGF-1 signaling[10]—all of which extend healthy lifespan.
2. Restricting Specific Amino Acids: Target the Key Culprits
If protein restriction delivers tangible anti-aging benefits for middle-aged people, does this mean we only need to restrict total protein intake? Not quite! Behind the "high-protein accelerates aging" phenomenon, we need to identify the specific substances driving this response[11]—to "target the key culprits."
Below are two major classes of amino acids that years of academic research have identified as the most likely "key culprits." Properly controlling their intake may yield twice the result with half the effort.
No. 1: Methionine Restriction—A Multi-Pronged Approach to Longevity
As one of the essential amino acids for humans, methionine (also known as methionine) is abundant in legumes, fish, and dairy products. Restricting its intake has been shown to significantly extend the lifespan of various model organisms[12-14].
For instance, as early as 1993, researchers explored the anti-aging effects of methionine restriction in rats. When lifelong methionine intake was reduced from 0.86% to 0.17% (an approximately 80% decrease), the lifespan of male rats was extended by nearly 30%—and this "reduced intake" did not affect the rats’ normal growth[15].
The benefits of methionine restriction are no accident; they stem from its regulation of multiple biological processes in the body:
- The methionine codon is identical to the initiation codon for protein translation (both AUG). Restricting methionine intake significantly downregulates protein synthesis, avoiding the accumulation of errors caused by frequent synthesis[16].
- Methionine can increase energy expenditure by regulating the level of the hormone FGF21[17].
- Methionine metabolites (SAM, or S-adenosylmethionine, and cysteine) regulate histone and DNA methylation in the body and influence oxidative stress levels[8].
- Methionine restriction also effectively activates the well-known AMPK longevity pathway[18].
Even more notably, methionine may be the "ultimate answer" behind the anti-aging effects of caloric restriction (the "king" of anti-aging diets). A landmark 2020 study jointly published by Tsinghua University and Peking University showed that when methionine was supplemented to yeast under caloric restriction, the lifespan-extending effect of caloric restriction disappeared[19].
In the fight against aging, "methionine restriction" uses a multi-pronged strategy to pursue longevity.
No. 2: BCAA Restriction—Putting the Brakes on mTOR for Lifespan Extension
BCAAs (branched-chain amino acids) are not a single amino acid, but a collective term for leucine, isoleucine, and valine. First detected in excessive amounts in the blood of obese people in the 1960s[20], they were later found to be closely associated with age-related insulin resistance and identified as one of the possible pathogenic mechanisms of type 2 diabetes[2, 21].
For those familiar with anti-aging research, seeing a substance labeled as an "mTOR activator" often links it to "accelerated aging" by instinct. As potent activators of the mTORC1 complex, excessive BCAA intake not only causes increased fat mass, hyperphagia, and insulin resistance—it also leads to the "severe side effect" of accelerated aging[2, 22, 23].
In contrast, BCAA restriction has been shown to:
- Increase the survival rate of progeric mice,
- Improve metabolism in wild-type mice,
- Extend their lifespan by 30%[24].
Conversely, excessive BCAA supplementation in the diet induces hyperphagia and shortens lifespan in mice[22].
These "life-extending" effects occur because controlling BCAA intake applies a moderate "brake" to mTORC1[8], allowing cells and the body to extend their healthy period in a sustainable way. The Confucian concept of the "Mean" (Zhongyong) seems surprisingly applicable to explaining this anti-aging mechanism.
3. How to Implement Protein/Amino Acid Restriction?
At this point, some readers may be eager to ask: "Does this mean we can’t eat protein or methionine at all?" The answer is clear: "Of course not!"
- Protein, as one of the three major nutrients, is a fundamental component of organisms.
- Methionine and BCAAs are essential amino acids that the human body cannot synthesize on its own—we would lack them if we don’t consume them.
A deficiency in any of these would immediately trigger "alarms" in the body.
As shared in earlier discussions about anti-aging diets: "Restriction does not mean elimination; it means eating correctly, choosing the right foods, and sticking to it consistently." This is not only a reflection but also a personal practice in daily life.
So, for protein/amino acid restriction, how should we eat correctly? How much should we eat? What should we eat? Or how can we assess if this approach is suitable for us?
References
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