Supplement Boosts Lifespan by 72%! West China Hospital Study in Nature Sub-journal: This Muscle-Building Compound May Shorten Lifespan — Metabolism Is the Key!

Glutamine, which is Springjia’s main product, is a staple on many fitness enthusiasts’ supplement checklist. After an intense workout, a couple of scoops help ease muscle soreness and support immune function. As the most abundant free amino acid in the human body, it also repairs intestinal barriers, fights oxidative stress, and is even used as a supplement to support gut health and immunity in pets[1].

Yet this daily go-to supplement may carry hidden risks. A recent study from the National Clinical Research Center for Geriatric Diseases, West China Hospital, Sichuan University, published in a Nature sub-journal, found that glutamine fails to deliver anti-ageing benefits. Instead, dysregulated glutamine metabolism triggers the pro-ageing mTORC1 pathway and accelerates senescence!

Is ageing the root cause?

When people take glutamine, they expect it to repair the gut barrier, fuel immune cells, or mend damaged muscle fibres — and it can achieve all these effects. Once inside cells, glutamine is broken down by glutaminase 1 (GLS1) into glutamate and ammonium. Part of these products enter the tricarboxylic acid cycle to generate cellular energy, while the rest serves as raw material for synthesising glutathione, the powerful antioxidant. All sounds promising.

However, researchers from West China Hospital discovered that glutamine metabolism follows a completely different, detrimental route in senescent cells compared with young cells.

The team compared metabolites between senescent and young cells across three cell models. They identified 88 metabolites with elevated levels in senescent cells, most of which were amino acids. Glutamine stood out as the core metabolite in this altered metabolic network.

Figure note: Most metabolites upregulated in senescent cells are amino acids; glutamine occupies a central position in the metabolic network.

GLS1, the enzyme responsible for glutamine breakdown, also showed drastically higher expression and activity. In short, senescent cells consume glutamine at an excessive rate.

Figure note: Glutaminase protein expression and enzyme activity are far higher in senescent cells than in young cells.

This pattern also holds in living organisms. In aged mice equivalent to humans in their 80s, GLS activity rises sharply in the kidneys, spleen and especially muscle tissue.

Figure note: Increased enzyme activity observed in the kidneys, spleen and muscle of 27-month-old aged mice.

You may wonder: glutamate produced from glutamine breakdown is the precursor of glutathione, so why does this drive ageing?

The answer lies in the metabolic divergence between young and aged bodies at the final step of glutathione synthesis. GCL is the rate-limiting enzyme for glutathione production. Unlike GLS1, GCL activity plummets with ageing. As a result, large amounts of glutamate keep being generated upstream, yet downstream glutathione synthesis cannot keep up, causing glutamate accumulation.

Beneficial metabolites turn harmful

Where does the accumulated glutamate go? The research traced the metabolic fate: excess glutamate and ammonium (NH₄⁺) from continuous glutamine breakdown undergo a series of reactions and get converted into arginine inside cells.

Figure note: Glutamine catabolism splits into two branches, leading to arginine synthesis.

Consistently, researchers detected markedly elevated arginine levels in naturally aged fruit flies (60 days old) and 27-month-old aged mice.

Figure note: Arginine concentrations are significantly higher in naturally aged fruit flies and aged mice compared with young controls.

Arginine is widely recognised as a beneficial nutrient. It supports nitric oxide production to dilate blood vessels and protect cardiovascular health, stimulates growth hormone release, aids muscle growth and offers other well-documented benefits[3].

Nevertheless, excess arginine becomes problematic. Massive accumulated arginine activates mTORC1, the pro-ageing protein complex in the mTOR pathway — the same target inhibited by rapamycin.

Persistent abnormal activation of mTORC1 suppresses cellular autophagy. Damaged proteins and organelles build up continuously, driving multi-system ageing and creating a vicious cycle of senescence.

Can blocking overactive glutamine metabolism break this cycle?

Regulate supply and consumption — blocking is not the only solution

The researchers tested three strategies to inhibit excessive glutamine catabolism:

• Restrict supply: Culture cells in a glutamine-depleted environment
• Chemical inhibition: Use inhibitors DON and CB-839 to suppress glutaminase
• Genetic suppression: Reduce expression of the GLS1 gene

All three interventions reduced senescent cells. Senescent cells stained blue were fewer. Levels of p16, a core senescence marker, dropped substantially. Pro-ageing and pro-inflammatory factors including Cxcl10, Tnf, Il6 and Mmp9 also decreased.

Figure note: Blue staining marks senescent cells (SA-β-gal staining). Treatment with DON reduced senescent cells and lowered levels of the key senescence protein p16.

Experiments on fruit flies further demonstrated striking results: Fruit flies with knocked-down GLS1 expression had their median lifespan extended from 59 days to 102 days, and maximum lifespan from 116 days to 147 days — nearly a 72% increase in median lifespan.

Longer lifespan came with better physical function: the flies showed enhanced climbing and locomotor capacity, plus improved intestinal barrier integrity.

Figure note: GLS1 gene knockdown shifts the lifespan curve rightwards, improves climbing performance and alleviates intestinal damage.

On the contrary, supplementing healthy young fruit flies with high doses of glutamine or arginine shortened their lifespan significantly. Both 20 mM and 100 mM concentrations reduced lifespan, with the 100 mM group showing the strongest negative effect.

Figure note: High-dose glutamine and arginine supplementation shortened the lifespan of healthy young fruit flies.

Does this mean older adults should avoid glutamine and arginine supplements to prevent accelerated ageing? Fitness lovers may feel alarmed, yet there is no need for panic.

The 100 mM amino acid concentration used in fly studies is extremely high, far exceeding normal dietary intake. Translated to human equivalents, this would mean a 60 kg adult consuming an extra 30 g to 50 g of pure glutamine or arginine powder per day — a dosage almost no one reaches in daily supplementation.

The culprit is not glutamine or arginine themselves, but the dramatic metabolic differences between young and aged bodies.

To sum up: young people who keep regular strength training can continue glutamine supplementation as needed. However, older adults with declining physical function should avoid high-dose amino acid supplements blindly.

Maintaining resistance training may help reroute glutamate and arginine towards their intended physiological roles: repairing muscle, boosting immunity and preserving intestinal integrity.