A Short One (about a Long Subject)
A formal demonstration of the healthspan- and lifespan-extending effects of rutin on mammals
I happily found this 2021 article last evening, after supper and after a day of constructing and installing a short set of steps for the back deck of our eventual retirement house.
From the article:
Ageing is one of the most challenging issues in the fields of population and health research nowadays. Here, we demonstrated that chronic sodium rutin treatment significantly extended the lifespan in wild-type C57BL6 mice by 9.3% and, more importantly, increased the health span by significantly delaying ageing-related morphological changes. Those results were consistent with the previous report that rutin promote longevity in Drosophila melanogaster (Chattopadhyay et al., 2017). Our study for the first time demonstrated this effect in mammals. Furthermore, whole-body metabolic investigations, metabolomics and transcriptomics revealed that sodium rutin treatment promoted liver fitness by modulating lipid metabolism. We also demonstrated that the hepatoprotective effect of sodium rutin was achieved by enhancing hepatocytic autophagy. Thus, our study strongly implicates that sodium rutin is a promising drug candidate for targeting ageing.
Ageing is a process of progressive impairment of homeostasis at the genomic, cellular, tissue and whole-organism levels, increasing the risk of diseases and death (Timchenko, 2009). At the cellular level, multiple biological alterations accumulate over time, including genomic stability, epigenetic alterations, telomere attrition, loss of proteostasis, dysregulation of nutrient sensing, altered intracellular communication, mitochondrial dysfunction, stem cell exhaustion and cellular senescence. The crosstalk between the ageing-related dysfunction and metabolism dysregulation had been reported in previous studies (López-Otín, et al., 2016). At the whole-organism level, the ageing phenotypes usually comprise lower voluntary running, lower energy expenditure, glucose intolerance and reduced fatty acid oxidation (Azzu & Valencak, 2017). In our study, all the above ageing-related phenotypes were significantly reversed by sodium rutin treatment. The liver is the central organ for metabolic homeostasis and liver fitness reportedly plays an important role in the anti-ageing effects of nutritional interventions, such as caloric and protein restrictions (Jové et al., 2014; Vermeij et al., 2016). In accordance, we found that sodium rutin markedly promoted liver metabolic fitness and alleviated ageing pathological features in aged mice.
Low grade inflammation is a hallmark of ageing. In this study, our transcriptomic analysis showed that sodium rutin treatment has an anti-inflammatory effect in liver. According to gene ontology analysis, the genes involved in inflammation pathway were significantly downregulated in sodium rutin treatment group (Figure 4d). Actually, our previous work showed that sodium rutin treatment exhibits neuroprotective property by suppressing microglia-derived proinflammatory cytokine production and enhancing microglia phagocytosis (Pan et al., 2019). Here, we also observed that sodium rutin treatment reduced the number of senescent cells in vivo (Figure 2o – q). Together, our data indicated sodium rutin treatment could alleviate senescence-associated secretory phenotype. Thus, we argue sodium rutin confers a senolytic property.
Rutin doses used in the mouse study followed the normal clinical rutin dosing rate range used in humans for correction of hemorrhoids, varicose veins, and lower leg swelling of 3mg/kg/day to 14mg/kg/day. Note that Mahric (1991) reported the use of rutin in women at 4 grams per day. Assuming an average adult female body weight of 125 pounds, this corresponds to a rutin dosing rate of about 70mg/kg/day — or about in the neighborhood of the amount of rutin historically taken in each day by the bitter buckwheat-eating Burusho during the late winter-spring lean times of each year.