Barking up the Right Tree: Phlorizin, a Component of Fruit Tree Bark, Supports Healthy Aging in Mice
Few things are hotter in the aging and longevity research field than the search for natural substances that support healthy aging. Phlorizin – a naturally occurring product found in the bark of apple, pear, cherry, and other fruit trees – lowers blood sugar levels and has been demonstrated to have antioxidant properties.
Research from Jilin Agricultural University in Changchun, China, shows that phlorizin supports brain health and cognition in aging mice. The Chinese researchers think this happens by phlorizin’s effects on gut microbiota; they think that the gut-brain axis may hold a key role in phlorizin-induced effects on healthy aging. "We reported that phlorizin minimized neuro-inflammation, nerve cell [death], and memory impairment in an animal model of aging," wrote senior author Wencong Liu and colleagues. “We also found that phlorizin played an important role in improving the function of the microbiota-gut-brain axis in mice with aging.”
Phlorizin Supports Cognitive Function During Aging
Good hippocampal function is necessary for both spatial working and reference memories. Accumulating research has confirmed that hippocampal damage can cause memory impairment. Aging is closely related to hippocampal damage, which often occurs together with physical weakness, physiological deterioration, reduced learning ability, and cognitive decline, in addition to other risks associated with aging.
The present study was performed using a common approach – the 8-arm maze test – to assess learning and memory retention in mice. The results demonstrated that aging triggered spatial memory impairment in the animals, but the behavioral indexes were significantly improved in mice treated with phlorizin, suggesting that phlorizin could improve memory and learning abilities.
To explore how phlorizin was working to support healthy aging, Wencong Liu and colleagues looked at levels of proteins related to inflammation and cell death in the brain. Tissue from aged mice showed a decrease in neurons and an increase in the level of proteins related to cell death. With phlorizin treatment, however, this was significantly reversed, suggesting that phlorizin exerts an anti-cell death effect on the brain.
The Chinese researchers also detected the activity of antioxidant enzymes in mouse blood serum, liver, and brain samples. The results showed that aging significantly affected the antioxidant enzyme levels and activity in mice. However, with the increase in phlorizin therapeutic concentration, these indicators underwent significant changes in a dose-dependent manner – greater doses of phlorizin led to greater increases in antioxidant levels and activity. These results indicate that phlorizin can enhance the antioxidant capacity of aging mice, which may be related to how it supports healthy aging.
Phlorizin Works Through the Microbiome-Gut-Brain Axis
The relationship between aging and the gut microbiome is a two-way interaction, and so too is that of aging and inflammation. Gut microbes use dietary fiber as a fermentation substrate to produce a large amount of short-chain fatty acids. These metabolites are neeeded to keep inflammation and the process of aging in check. Changes in the structure and diversity of the gut microbiota have been associated with oxidative and inflammatory processes in the aging brain through the gut-brain axis.
The microbiome associated with aging includes beneficial bacteria, such as bacteria that produce short-chain fatty acids (Lactobacillus, Bacteroides), and relatively pathogenic bacteria (Fusobacterium, Parabacteroides). Studies have shown that probiotics represented by lactic acid bacteria can effectively delay aging, which provides a reference for research on how to support healthy aging by adjusting the diet structure. Lactobacillus is friendly to humans, and additional supplementation of Lactobacillus products might improve systemic immunity to ameliorate aging. Bacteroides possess similar effects and is often included in functional foods.
In this study, phlorizin shifted the intestinal flora towards species related to antioxidant and anti-inflammatory processes. Phlorizin effectively elevated the abundance of gut microorganism-generated short-chain fatty acids, especially from Lactobacillus and Bacteroides. In particular, the short-chain fatty acids generated by Lactobacillus could stimulate antioxidant enzyme levels, while those of Bacteroidales seem to relieve intestinal inflammation. Therefore, the treatment of phlorizin improved the relative abundance of beneficial bacteria in the intestines of mice, inhibiting the growth of harmful bacteria, which was conducive to supporting brain health and cognition in aging mice.
What Effect Does Phlorizin Have On People?
While we don’t yet know how phlorizin may affect brain health and cognition in aging people, a 2015 study looked into the ability of phlorizin to lower high levels of blood sugar in healthy volunteers. The researchers prepared a low-sugar, fiber- and phlorizin-enriched powder from unripe apples and found that the dried and powdered pomace of unripe apples can be used as a health-promoting natural product for the reduction of major increases in blood sugar levels after eating. More studies are needed to cover a wider and more diverse cohort to better understand how much phlorizin someone may need to take to support healthy blood sugar regulation, let alone supporting brain health and cognition in aging people. But although we need more research, it does seem like consuming (the bark of) an apple per day could keep help keep the doctor away.
Chen H, Dong L, Chen X, et al. Anti-aging effect of phlorizin on D-galactose-induced aging in mice through antioxidant and anti-inflammatory activity, prevention of apoptosis, and regulation of the gut microbiota. Exp Gerontol. 2022;111769. doi:10.1016/j.exger.2022.111769
Makarova E, Górnaś P, Konrade I, et al. Acute anti-hyperglycaemic effects of an unripe apple preparation containing phlorizin in healthy volunteers: a preliminary study. J Sci Food Agric. 2015;95(3):560-568. doi:10.1002/jsfa.6779