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.

Mitochondrial Lon protease - depleted HeLa cells exhibit proteome modifications related to protein quality control, stress response and energy metabolism

“…Results, presented in figure 1E and F, show that Lon knockdown is associated with an increase in each parameter, in both glucose and galactose conditions. Regarding the increase in ROS and carbonylation levels in galactose compared to glucose medium, these results are consistent with those found when galactose was used to instigate aging in various models [31].…”

Wnt/β‐catenin/RAS signaling mediates age‐related renal fibrosis and is associated with mitochondrial dysfunction

“…To further elucidate the correlation between Wnt/β‐catenin signaling and mitochondrial dysfunction in age‐related renal fibrosis, we performed a study in C57BL/6 mice by injection of d ‐galactose ( d ‐gal), an accelerated aging model that has similarities to natural aging in rodents (Bo‐Htay, Palee, Apaijai, Chattipakorn, & Chattipakorn, ). The plasmid pV5‐sKlotho for secreted Klotho, an anti‐aging protein that serves as an endogenous Wnt antagonist (Zhou et al, ), was injected by hydrodynamic‐based gene delivery, an approach that is commonly used to ectopically express proteins in liver and kidneys (He et al, ; Zhou, Li, et al, ; Zhou et al, ; Zhou, Mo, et al, ).…”

“…It is notable that the administration of d ‐gal dramatically induced cellular senescence (Figure k). The reason behind this maybe that chronic d ‐gal exposure augments senescence‐related signals by reacting with the free amines of amino acids to form advanced glycation end products (AGE) (Bo‐Htay et al, ), a strong trigger of oxidative stress and inflammation, the two main mechanisms of aging (Feng et al, ; Zhou et al, ). We then checked the effect of Klotho.…”

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

“…Reactive oxygen species is the generic term for molecules or ions with high chemical and oxidative activities; excessive ROS in cells may cause damages to biomacromolecules, such as proteins, and thereby influence the normal functions of cells . Galactitol accumulation, antioxidant enzyme reduction and nonenzymatic glycation (NEG) initiation are three major mediating factors of D‐gal on cell and organ aging, and these three factors will eventually lead to an increase in intracellular ROS levels . According to our previous studies, ROS is an important factor that influences the senescence of MSCs.…”