Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: A systematic review

Background: Cellular senescence 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. This systematic review examined the association of dietary ingredients with cellular senescence in animals and humans, with an intent to identify dietary ingredients with senotherapeutic potential. Methods: This systematic review was registered at PROSPERO International prospective register of systematic reviews (Reg #: CRD42022338885). 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 animals investigating the effects of dietary ingredients via oral administration on cellular senescence load were included. 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, 83 articles consisting of 78 animal studies and 5 human studies aimed to reduce cellular senescence load using dietary ingredients. In animal studies, the most-frequently used senescence model was normative 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 five 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 ingredients with senotherapeutic potential in humans are limited and translation is highly warranted.