The notion that reducing food intake could enhance longevity has existed for millennia. The ancient Greek physician Hippocrates famously stated, “If you overnourish the patient, you nourish the disease as well. Excess is contrary to nature.”

For decades, scientists have been investigating the validity of this advice.

The first major evidence emerged in the 1930s when American nutritionist Dr. Clive McKay discovered that rats on a restricted diet lived nearly twice as long as those with unrestricted access to food.

These rats did not suffer from constant hunger nor did they struggle for survival. On the contrary, they exhibited better health in old age, showcasing improved lung and kidney function, with no signs of cancer (until their food supply was increased post-experiment).

Since then, calorie reduction has been linked to increased lifespan and health across various life forms, including single-celled organisms, nematodes, flies, spiders, grasshoppers, guppies, trout, mice, hamsters, and dogs.

Why is this the case? The theory suggests that reduced food consumption activates a biological mechanism in your cells that encourages energy conservation.

When food is scarce, expending energy for activities like reproduction becomes counterproductive, especially in an environment lacking sufficient resources.

Thus, evolutionary biology suggests that animals in such circumstances should conserve energy, slowing their aging process until food availability improves, increasing their chances of remaining healthy enough to reproduce later.

Anti-aging effects of eating less

While there is ample evidence of caloric restriction in animals, obtaining reliable human data poses challenges.

Funding bodies, ethics committees, and participants are understandably hesitant to commit to long-term dietary interventions.

The most significant trial to date is the carrie trial (A Comprehensive Assessment of the Long-Term Effects of Reducing Energy Intake), where participants aimed to cut their intake by 25% over two years.

(Ultimately, the average reduction was only 12 percent, highlighting the difficulty of maintaining such a regimen, even with scientific support.)

Though two years is insufficient to conclusively determine longevity, participants did experience an average weight loss of 8 kg (17.6 lb), along with minor reductions in LDL cholesterol, blood pressure, blood sugar levels, and inflammatory markers.

Cutting back on protein

If you wish to apply this concept personally, an important question arises about what exactly should be reduced in your diet.

Recent studies indicate that a reduction in protein intake—the critical factor influencing our health—may be essential.

For example, one study by researchers at the University of Sydney found that mice on a low-protein diet lived approximately 30% longer than those on a protein-rich diet.

Specificity matters here. Since proteins are composed of 20 amino acids, reducing one or more of these could potentially extend lifespan.

Research indicates that lowering levels of “branched-chain” amino acids (BCAAs) might extend male mice lifespan by 30%. (The reasons behind the different effects in female mice remain unclear.)

In fact, reducing the specific amino acid isoleucine resulted in a 33% increase in male mice lifespan (compared to just 7% for female mice).

Ongoing research is investigating additional amino acids. For instance, methionine presents a delicate case.

Mice consuming a diet with 0.15% methionine lived 10% longer than those on a standard diet containing 0.4% of this amino acid.

Conversely, mice consuming 0.1% methionine often faced early death from rectal prolapse, prompting one to consider the risks involved.

Current research is shifting focus from merely restricting dietary components to optimizing them. However, with 20 amino acids, the permutations can be overwhelming.

Even experimenting with simple combinations of high and low doses of each amino acid could require over a million trials.

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Genome-based amino acid diet

To tackle this complexity, scientists are examining our DNA, which directs protein synthesis. The building blocks of proteins are amino acids.

What if we provided living organisms with a diet that reflects the amino acid ratios found in their DNA?

Early research on fruit flies showed that those fed a diet aligned with their DNA ratios were larger, matured faster, laid more eggs, and had longer lifespans compared to those on standard diets.

A subsequent study involving mice found that when provided with the ideal dietary amino acid balance via their DNA, the mice demonstrated faster growth, increased muscle mass in males, and enhanced sperm production.

However, it’s yet to be determined if these mice will also enjoy prolonged lifespans.

While the biological effects of reducing protein intake remain uncertain, scientists are making strides in understanding the underlying mechanisms. Similar to calorie restriction, this approach appears to significantly slow down the aging process.

A recent study published in May 2025 suggests that a low-protein diet may help in reducing DNA damage and mutations.

This doesn’t imply that proteins are directly mutagenic, but their influence on metabolism might lead to the production of “free radicals” that can harm DNA and cellular structures.

DNA mutations are known precursors to cancer and have long been associated with the aging process.

The exploration of how dietary adjustments can indirectly influence the rate of chemical “errors” in our DNA is a promising area for research.

Not everyone needs protein reduction

So, should you begin reducing your protein intake? While animal studies provide compelling evidence, human research yields more nuanced findings.

One 2014 study found that individuals consuming less protein tend to live longer than those with high protein intakes. A 50-year-old consuming under 45 g (1.6 oz) of protein daily may expect to live approximately four years longer than someone consuming 90 g (3.2 oz) daily.

Nonetheless, generalizing this advice proves challenging. In individuals over 65, the same study indicates the opposite effect. This might be due to age-related muscle loss, where protein consumption aids in weight gain.

Moreover, individuals consuming a higher proportion of plant-based protein did not face an increased mortality risk during midlife.

Hence some contend that risks may stem more from excessive red and processed meat intake than protein consumption itself.

Another factor could be that plant proteins are generally lower in certain amino acids, like methionine, meaning high vegetable consumers might naturally have a lower methionine intake.

Sadly, no comprehensive human studies have been conducted to deliberately restrict specific amino acids.

However, it would be intriguing to research this approach in humans, not through protein powders but via dietary combinations that adhere to our genetic requirements and can be easily integrated into daily nutrition.

Such findings may help mitigate the downsides associated with strict diets. Reducing food variety often leads to reported feelings of hunger, chills, decreased libido, irritability, and slower recovery from injuries.

As an old saying in longevity science goes, while dietary restrictions might not extend your life, they can certainly make your life feel longer.

Medication alternatives to protein restriction

Perhaps the answer lies not in our kitchens but in pharmaceuticals. A drug called rapamycin, for example, activates cellular recycling pathways that mimic those triggered during dietary restriction, leading to lifespans increased by up to 60% in mice.

Diabetes medications that lower blood sugar are another avenue to induce caloric reduction and extend mouse lifespans.

Moreover, GLP-1 agonists such as semaglutide (Ozempic) have showcased the potential to alleviate various conditions by directly curbing appetite.

Could these or other medications help us maintain health without adhering strictly to lengthy dietary regimens?

As a person interested in a long, healthy life, but wishing to avoid being a hungry centenarian, I eagerly anticipate the initiation of clinical trials.

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