The therapeutic effect of diet and dietary ingredients on cellular senescence in animals and humans: A systematic review

Background Cellular senescence is a permanent state of cell cycle arrest and has been regarded as a therapeutic target for ageing and age-related diseases. Several senotherapeutic agents have been proposed, including compounds derived from natural products which hold the translational potential to promote healthy ageing. It is largely unclear whether cellular senescence could be targeted by dietary interventions. This systematic review examined diets and dietary ingredients and their association with cellular senescence load in animal models and humans, with an intent to identify dietary interventions with senotherapeutic potential. Methods The databases PubMed and Embase were systematically searched for key terms related to cellular senescence, senescence markers, diets, nutrients and bioactive compounds. Intervention and observational studies on human and animal models investigating the effects of diets or dietary ingredients via oral administration on cellular senescence load were included. The studies were screened using the Covidence systematic review software. Study design, methods and results were extracted. Biomaterials used for senescence detection were categorized into physiological systems. The SYRCLE’s risk of bias tool and Cochrane risk of bias tool v2.0 were used to assess the risk of bias for animal and human studies respectively. Results Out of 5707 identified articles, 82 articles consisting of 78 animal studies and 4 human studies aimed to reduce cellular senescence load using dietary interventions. In animal studies, the most-frequently used senescence model was normal ageing (26 studies), followed by D- galactose-induced models (17 studies). Resveratrol (8 studies), vitamin E (4 studies) and soy protein isolate (3 studies) showed positive effects on reducing the level of senescence markers such as p53, p21, p16 and senescence-associated ß-galactosidase in various tissues of physiological systems. In three out of four human studies, ginsenoside Rg1 had no positive effect on reducing senescence in muscle tissues after exercise. The risk of bias for both animal and human studies was largely unclear. Conclusion Resveratrol, vitamin E and soy protein isolate are promising senotherapeutics studied in animal models. Studies testing dietary interventions with senotherapeutic potential in humans are limited and translation is highly warranted.