Whether it be for gaining mass or losing weight, high-protein diets have been touted as part of the solution. However, the science increasingly shows that consuming too much protein is antithetical to longevity. This includes a new study by researchers from the Oncode Institute in the Netherlands showing that high protein intake shortens the lifespan of mice. 

High Protein Intake Shortens Mouse Lifespan

Countless studies of multiple organisms have shown that dietary restriction —reduced food intake without malnourishment—prolongs lifespan. However, since it is difficult to follow such a strict diet for an extended period of time, scientists have searched for the underlying processes that drive dietary restriction’s anti-aging effects. 

In doing so, the Dutch researchers previously showed that dietary restriction profoundly prolongs the lifespan of mice lacking DNA repair. Namely, in response to a 30% reduction in food intake, these DNA-repair-deficient (DRD) mice lived 3-fold longer. Based on these findings, the Dutch researchers used DRD mice to test the effects of a high-protein diet on lifespan. 

Strikingly, it was found that a low-carbohydrate, high-protein diet shortened the lifespan of male DRD mice by about 18% and female DRD mice by about 36%. In contrast, a low-fat, high-carbohydrate diet or a low-protein, high-carbohydrate diet had no significant effect on lifespan. Considering that low-carbohydrate diets are metabolically beneficial, these findings suggest that high protein intake shortens lifespan. Similar results have been observed in normal mice with intact DNA repair. 

(van Galen et al., 2026) Low-Carbohydrate/High-Protein (LCHP) Diet Shortens Lifespan. Left: The macronutrient composition of the LCHP, low-fat/high-carbohydrate (LFHC), and low-protein/high-carbohydrate (LPHC) diet, relative to a normal control diet. Right: The survival curves for male and female mice showing that only the LCHP diet shortens lifespan. Also, 30% DR extends lifespan beyond all other mice in females.

Protein Restriction Extends Lifespan 

The researchers also tested the effects of reducing protein intake on the lifespan of DRD mice. Interestingly, they found that reducing protein intake by 50%, but not 30% or 80%, extended the lifespan of male mice by 19%. In another group of mice, reducing protein intake by 93% extended lifespan by 15%, and reducing it by 95% shortened lifespan by 12%. While the 95% reduction likely shortens lifespan due to amino acid deficiencies, more studies are needed to make sense of why only certain reductions in protein intake extend lifespan. 

High Protein May Overwork Mitochondria and Elevate Inflammation 

To explore how high protein intake could be shortening the lifespan of mice, the Dutch researchers examined the genes of the liver. They found that many genes were altered by the low-carbohydrate, high-protein diet compared to the low-protein, high-carbohydrate diet. For example, high protein increased genes involved in mitochondrial function and decreased genes involved in inflammation. 

These findings suggest that mitochondria are overworked when high levels of protein are consumed. When mitochondria are overworked, they generate excess levels of reactive oxygen species (ROS). In excess, ROS cause damage to cellular components, such as DNA, in what is called oxidative stress. Oxidative stress is a biological driver of aging, much like inflammation, which was shown to be elevated in response to high protein.

(van Galen et al., 2026) Low-Carbohydrate/High-Protein (LCHP) Diet Increases Mitochondrial Function and Inflammatory Genes. The left side of each graph shows which genes are elevated in response to the LCHP diet, while the right side shows which genes are elevated in response to a low-protein/high-carbohydrate (LPHC) diet.

High Protein Is Associated with Transcriptional Stress 

Whether overworked mitochondria are the trigger for oxidative stress and inflammation in response to high protein intake needs further study. However, the researchers discovered clues that point to this being the case. When DNA is damaged, it can cause a disruption in the transcription of genes (where DNA is transcribed into mRNA). When this occurs, longer genes are more susceptible to disruptions that lower mRNA levels. These transcriptional disruptions have been shown to increase with aging and contribute to the aging process. 

With this in mind, the researchers measured mRNA levels and sorted them by length. Remarkably, they found that the low-carbohydrate, high-protein diet was associated with the downregulation of longer genes. To determine if this occurs in normal mice, the researchers analyzed data from a previous study by Dr. Speakman and team. In Speakman and team’s study, mRNA was measured from a region of the brain called the hypothalamus, which is the body’s control center. Moreover, the diet used in Speakman’s study was more realistic, as a 30% protein diet was compared to a 5% protein diet in normal mice. Still, under these conditions, the Dutch researchers again found a downregulation of longer genes in response to a high-protein diet.

(van Galen et al., 2026) High Protein Reduces the Transcription of Long Genes. In the hypothalmi of a common lab mouse strain (C57BL/6J), the high protein diet was associated with expression of shorter genes.

Together, these findings point to the following model, which may at least partially explain how high protein intake shortens lifespan: The oxidative stress from overworked mitochondria triggers DNA damage, which then causes transcriptional stress, leading to the downregulation of longer genes. Many long genes make proteins that regulate metabolism and are linked to longevity, including mTOR (mechanistic target of rapamycin) and IGF (insulin-like growth factor). It follows that a reduction in these genes could promote accelerated aging and a shortened lifespan. 

Does Too Much Protein Shorten the Lifespan of Humans?

Whether a high intake of protein shortens the lifespan of humans will likely not be studied directly. However, there are human studies suggesting that consuming a low-carbohydrate, high-protein diet leads to a shorter life. For example, a meta-analysis of 17 studies concluded that high protein increases the risk of all-cause mortality by 31%. Moreover, protein is known to activate mTOR, which becomes overactive in old age, contributing to a shortened lifespan. 

On the other hand, older individuals often benefit from increased protein intake to support muscle health. Adequate muscle mass is a key indicator of longevity that is supported by the consumption of protein. Therefore, it could be that too much protein accelerates aging, but just enough protein supports healthy aging. Nevertheless, the precise level of protein intake necessary to promote healthy aging while still maintaining muscle mass will likely continue to be debated.