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The less you eat, the longer you live! The first human controlled trial proves the mechanism, 14% calorie restriction can really prolong healthy lifespan

When it comes to caloric restriction (CR) , people often associate it with “weight loss”. But don’t be so limited, the benefits of CR go far beyond weight loss!

A large number of studies have confirmed that, under the condition of fully guaranteeing nutrients (such as essential amino acids, vitamins, etc.) , limiting the total daily intake of energy can really improve health conditions and even achieve the purpose of “life extension”.

However, those who follow CR research have felt that most of the previous experiments were based on animals rather than humans. Rodent experiments have shown that 40% of the CR model can induce negative energy balance to inhibit inflammation and reduce the burden of disease, thereby extending the lifespan of mice. (For details, see: Calorie restriction can not only delay aging, inhibit tumor growth, but also a natural “sunscreen”! )

But can such a CR model really be analogized to humans? With a 40% calorie restriction, it doesn’t matter whether you can continue your life or not, you may be “starving to live” first!

To test the feasibility of CR in humans and reveal the mechanisms behind its health benefits, a research team from Yale University conducted a genetic analysis of CR participants and compared them with a normal eating group. It was found that CR reduces the production of a stromal cell protein called SPARC in the body, thereby suppressing harmful inflammation, improving metabolic function, and extending healthy lifespan in old age. The study, the first randomized controlled study of CR in healthy humans , was published on August 12 in Immunity , a sub-journal of Cell .

Before launching the experiment, the researchers first thought about the question: Wouldn’t it be too extreme to extend the 40% CR model in mice to humans? What is the acceptable and most manageable caloric restriction for humans?

Based on a previous large 2-year caloric restriction RCT clinical trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy, CALERIE-II) , the researchers found that under free-living conditions, 14% of CR was acceptable in humans. acceptable, and can effectively reduce inflammatory markers in the blood.

Taking a normal person as an example, if the daily energy intake of this person is 1800kcal, 14% CR is 252kcal, which is about equal to an ice cream, 1/2 chocolate croissant, 50g potato chips, a small cream cake and so on. It is equivalent to cutting off daily snacks, which is still very acceptable.

To further assess the long-term effects and internal mechanisms of CR, the researchers divided the participants into two groups: the experimental group reduced energy intake by 14% per day for 2 years, while the control group ate a normal daily diet. At baseline, 1-year, and 2-year time points, participants’ abdominal subcutaneous adipose tissue was extracted for RNA sequencing to explore CR-induced genetic changes.

The results showed that ① After 1-2 years of CR, SPARC in the adipose tissue of the experimental group decreased significantly, and was significantly correlated with BMI, body fat percentage, leptin, C-reactive protein (CRP) , tumor necrosis factor-α (TNFα) , the reduction of integrin ICAM-1. ② Conversely, compared with relatively lean individuals, the amount of SPARC protein was higher in obese individuals.

Taking these two results together, the researchers speculate that SPARC is likely to be the BOSS protein behind the “damage to human health” that contributes to the increased inflammation associated with obesity.

SPARC protein pathway in humans
SPARC protein pathway in humans

SPARC, what protein? SPARC is the abbreviation of Secreted protein acidic and rich in cysteine, a cysteine-rich acidic secreted glycoprotein , which is related to the occurrence of obesity, diabetes and inflammation.

“Inflammation plays an important role in age-related decline, well-studied. But how does an intervention like CR work through SPARC to control inflammation?” To further understand the mechanism behind it, Yale University Vishwa The team of Professor Deep Dixit established a mouse model.

Unsurprisingly, SPARC protein in mice induces an interferon response in macrophages via glycolysis and IRF7, and converts originally anti-inflammatory M2 macrophages into pro-inflammatory phenotype M1 macrophages by activating TLR4, This promotes the occurrence of inflammation and causes health damage.

When the researchers compared SPARC adipocyte-deficient mice with normal controls, they found that reducing the SPARC protein produced by the mice’s adipocytes not only improved their glucose tolerance and insulin sensitivity, but more importantly, the frailty of the old mice in the experimental group The degree is significantly reduced (reflected in the vitality of the old mice , not only increased grip strength, but also can run wild on the rotating rod, which is a medical miracle) .

Clearly, in the case of limiting SPARC production, the metabolic dysregulation caused by aging in aged mice was alleviated and their healthy lifespan was extended!

Inhibition of SPARC reduces age-related increases in inflammation
Inhibition of SPARC reduces age-related increases in inflammation

Eh, in other words, restricting energy intake is meant to reduce the production of SPARC proteins, thereby suppressing harmful inflammation and extending healthy lifespan in old age. In the whole process, SPARC is the “culprit” that induces inflammation.

So, in practical applications, can we just induce SPARC to decrease and achieve life extension without changing calorie intake? This is also the focus of the researchers’ next research. Wouldn’t it be beautiful if it could really achieve “longevity without starvation”?

However, at this stage (before the research has progressed to the next step) , we can only eat one less snack every day, while enjoying the “thinness”, but also to continue the “high-quality” life for our old age~

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