Effects of d-galactose-induced ageing on the heart and its potential interventions

Abstract

Ageing is a strong independent risk factor for disability, morbidity and mortality. Post-mitotic cells including those in the heart are a particular risk to age-related deterioration. As the occurrence of heart disease is increasing rapidly with an ageing population, knowledge regarding the mechanisms of age-related cardiac susceptibility and possible therapeutic interventions needs to be acquired to prevent advancing levels of heart disease. To understand more about the ageing heart, numerous aged animal models are being used to explore the underlying mechanisms. Due to time-consuming for investigations involving naturally aged animals, mimetic ageing models are being utilized to assess the related effects of ageing on disease occurrence. d-galactose is one of the substances used to instigate ageing in various models, and techniques involving this have been widely used since 1991. However, the mechanism through which d-galactose induces ageing in the heart remains unclear. The aim of this review was to comprehensively summarize the current findings from in vitro and in vivo studies on the effects of d-galactose-induced ageing on the heart, and possible therapeutic interventions against ageing heart models. From this review, we hope to provide invaluable information for future studies and based on the findings from experiments involving animals, we can inform possible therapeutic strategies for the prevention of age-related heart diseases in clinical settings.

Keywords: ageing; d-galactose; heart; mitochondria.

Figure 1

Summary of how d‐galactose induces oxidative stress. Excess d‐galactose is reduced by galactose reductase to form galactitol which can lead to osmotic stress. Additionally, high level of d‐galactose can be oxidized by galactose oxidase to yield hydrogen peroxide; increased hydrogen peroxide causes a decrease in antioxidant enzymes (SOD). Furthermore, d‐galactose can initiate non‐enzymatic glycation reactions to form advanced glycation end products (AGEs) after weeks or months. When AGEs react with their receptors (RAGE), ROS production occurs through NADPH oxidase activation. H₂O₂, hydrogen peroxide; SOD, superoxide dismutase; RAGE, receptor for advanced glycation end products; ROS, reactive oxygen species.

Figure 2

Summary of how d‐galactose induces cardiac dysfunction in ageing heart models. In d‐galactose‐induced ageing heart models, increased cardiac senescence marker expression, increased oxidative stress, decreased antioxidant levels, increased inflammation, increased apoptosis and altered calcium homestasis lead to cardiac dysfunction.

Figure 3

Summary of potential interventions in d‐galactose‐induced ageing heart models. AOF, Alpinate Oxyphyllae Fructus; EGB761, Gingko Biloba extract; NaHS, sodium hydrosulphide; DO, Dendrobium Officinale; PCCL, polysaccharide isolated from the seeds of Cuscuta chinensis Lam; APC, anthocyanin from purple carrots.