According to a recent study, the ketogenic diet is shown to trigger cellular senescence but can be mitigated based on diet regimen.

The study, published in Science Advances, demonstrated that a ketogenic diet (KD) induced p53-dependent cellular senescence across multiple organs, including the heart and kidneys. The process is mediated through the activation of adenosine monophosphate–activated protein kinase (AMPK) and the inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and subsequent induction of p21.

Researchers employed two distinct diets with varying fat compositions on six mice of varying ages, a KD which included 90.5% calories from fat versus a control diet of 17% calories from fat. The researchers observed significant increases in markers of cellular senescence after 21 days on the KD. 

"As cellular senescence has been implicated in the pathology of organ disease, our results have important clinical implications for understanding the use of a KD,” said researchers.

However, the researchers also found that the KD-induced cellular senescence could be prevented by intermittent KD regimens and eliminated through the administration of the senolytic agent ABT-263. These findings suggest that, while KDs offer benefits such as weight loss and metabolic improvements, they may also pose risks of cellular senescence if not carefully managed.

To mitigate potential adverse effects, the researchers emphasized the necessity of individualizing KD protocols. They highlighted variables such as age, diet composition, and duration may significantly influence outcomes.

"An IKD [intermittent keto diet] could be especially relevant in the clinic, as this type of KD may be easier for patients to adhere to and could potentially offer many of the benefits of weight loss and improved health parameters without the risk of cellular senescence from sustained KD” researchers noted.

Whether and for what conditions an IKD would be most beneficial for humans, the researchers noted more research is needed.

Grants from the National Cancer Institute and the Cancer Prevention and Research Institute of Texas supported the study. The authors reported having no competing interests.