The impact of dietary restrictions on the expression of FOXO3 as an anti-ageing biomarker

Abstract

Ageing involves destruction on the molecular, cellular, and organ level, causing disease and death. Previous research has discovered that both diet and genetics can affect ageing. Forkhead helix box (FOXO) transcription factors are found to be the major transcription factors correlated with longevity. In addition, one of the best-known signals that are also capable to affect ageing is a dietary restriction (DR) which is evolutionary conserved. The objective of this paper is to expand our knowledge regarding the FOXO3 gene expression as anti-ageing biomarker, and how DR could impact its expression. This review was written through a rigorous searching process from various databases including Google Scholar, Science Direct, Scopus, and PubMed, by utilizing keywords such as the ‘anti-ageing’, ‘dietary restriction’ along with ‘forkhead box O3 gene’. FOXO3 exerts its essential role through the protein kinase B (Akt/PKB) signaling pathway, as well as post-translational modifications, further activating downstream target genes. This would result in cell apoptosis, cell cycle arrest, DNA repair, and other important physiological processes. Relating to diet, the FOXO3 gene is expressed when organisms face low nutrient availability. It can also be downregulated by reducing the amount of circulating insulin-like growth factor 1 (IGF-1) level which can be achieved through fasting. Meanwhile, DR can enhance the FOXO3 expression, anti-ageing effects and further establish longevity. However, the research regarding the effect of DR in humans is still limited. Future studies need to investigate the optimal type of DR along with uncovering the molecular mechanism behind the FOXO3 expression and ageing.