·    Sodium rutin treatment extended the life and healthspan of mice.
·   The present findings suggest sodium rutin is a promising candidate for clinical application in age-related diseases.

Since aging is linked to progressive dysregulation of our metabolism, the maintenance of metabolic health may lead to anti-aging effects. Lifespan-extending strategies, such as dietary restriction and rapamycin treatment, have been reported to improve liver metabolism, indicating that liver health plays an important role in the anti-aging process. 

Li and colleagues from the Beijing Institute of Basic Medical Sciences show that sodium rutin — a salt version of a natural flavonoid compound that is widely distributed throughout the plant kingdom, especially in vegetables and fruits — significantly extended the lifespan and healthspan of mice by maintaining liver health. Continuous sodium rutin supplementation in drinking water significantly extended the lifespan in mice by roughly 10%, improved physical performance, and delayed aging characteristics. The present findings render sodium rutin a promising candidate for clinical application in aging-related diseases.

Rutin has anti-aging potential

Rutin — found in capers, olives, buckwheat, asparagus, and raspberries — has attracted attention over the past decades due to its multiple functions, including anti-oxidative, anti-inflammatory, anti-tumor, anti-diabetic, neuroprotective, and cardiovascular-protective effects. A recent study has shown that rutin is a metabolic modulator that ameliorates obesity in mice through brown fat activation. But the poor solubility of rutin in aqueous media hampers the thorough investigation of its biological mechanisms and its clinical application.

Sodium rutin extends the lifespan and healthspan of mice with beneficial effects on metabolism

To investigate the long-term effect of sodium rutin treatment on male mice, Li and colleagues added sodium rutin to drinking water (0.2 mg/mL). Mice had free access to sodium rutin supplemented water from 32 weeks of age to end of life. The research team found that the lifespan of sodium rutin-treated mice was significantly higher than that of untreated mice. The mean lifespan was increased by approximately 79 days in the sodium rutin-supplemented group and the maximum lifespan was increased by aging-related approximately 3 months.

(Li et al., 2021 | British Journal of Pharmacology) Chronic sodium rutin (NaR) treatment extends the lifespan of mice. (a) Survival curves for mice fed with normal water and NaR-supplemented water. (b) Average lifespans of untreated (Ctrl) and NaR-treated mice. (c) The maximum lifespan of untreated (Ctrl) and NaR-treated mice.

More importantly, sodium rutin increased the health span by significantly delaying aging-related changes, such as balding and skin aging. Sodium rutin also improved the performance of aging mice in several behavioral and physical exams, such as tests of spatial memory and balance.

(Li et al., 2021 | British Journal of Pharmacology) Chronic sodium rutin (NaR) treatment improves the health of aging mice. (b) The score of aging-related morphological changes (including kyphosis, cataract, baldness, each of which count 1 point, the range of aging score is 0 to 3 points. A higher score represents a more obvious aging trait). (c) Average speeds and (d) total distances of 14-month-old mice during the open-field test. (e) Falling latencies of 16-month-old mice in the rotarod test.

Li and colleagues looked into how sodium rutin was affecting the aging of cells and tissues. In 2-year old mice, sodium rutin treatment markedly reduced the accumulation of fat in the liver. They also detected a lower level of liver cell replicative arrest (senescence), reduced fibrosis in the heart, kidney scarring (glomerulosclerosis), and atrophy in the skeleton muscle in sodium rutin-treated mice. These results suggest that dietary supplementation with sodium rutin extends the lifespan, improves fitness, and effectively alleviates a range of aging-associated pathologies in mice.

(Li et al., 2021 | British Journal of Pharmacology) Chronic sodium rutin (NaR) treatment reduces cell senescence in aging mice. (o) β-gal staining of liver tissue for aged, non-proliferating (senescent) cells from 24-months-old control (Ctrl) and NaR-treated mice. (p) Statistic numbers and (q) areas of positive counts in senescent cells (β-gal) in liver tissue.

Furthermore, a whole-body investigation of metabolism and gene activity revealed that sodium rutin treatment promoted liver fitness by modulating lipid metabolism. The research team from the Beijing Institute of Basic Medical Sciences also demonstrated that the protective effect of sodium rutin on the liver was achieved by enhancing autophagy — the cell’s recycling process critical to metabolism and health — of liver cells.

“Our study strongly implicates that sodium rutin is a promising drug candidate for targeting aging,” proposed Li and colleagues. “We suggest that sodium rutin could be used in anti-aging therapy and for the treatment of aging-associated diseases.”