New Study Suggests Plant Fat Could Counter Aging by Reducing Harmful Bacteria from Gut

A high-fat diet significantly increases the lifespan of prematurely aged mice, restoring their blood glucose levels, reducing the spread of harmful bacteria, and reducing markers of aging.

Key Points:

A diet high in coconut oil increases the survival rate of prematurely aged mice by over 80% and improves blood glucose levels.
The high-fat diet reduces pathogenic gut bacteria like E. coli and the spread of harmful bacteria to the spleen, liver, and kidneys.
High coconut oil diet reduces spleen, liver, and kidney inflammatory markers and markers for senescent cells — cells that contribute to the aging process.

It is becoming increasingly clear that our gut microbiota — bacteria and other microorganisms that live in our gut — could contribute to how fast we age. Some gut bacteria are beneficial (probiotics), while others are harmful, and our diet can influence which gut microbiota reside in our body. Now, researchers from Tsinghua University in China have found that a high-fat diet influences the lifespan of prematurely aged mice by eliminating harmful bacteria.

Xu and colleagues report in Aging Cell that gut bacteria mediate the alleviation of premature aging with a high-fat diet. They show that a high-fat diet increases the survival rate of prematurely aged mice while improving their blood glucose levels. The high-fat diet reduces harmful gut bacteria and their spread to the internal organs, where they promote markers of aging, including inflammation and senescent cells.

“Our results provide a mechanism for the causal link between gut dysbiosis and aging, and support a beneficial effect of a high-fat diet for correcting gut dysbiosis and alleviating premature aging,” state Xu and colleagues.

Diet High in Coconut Oil Alleviates Premature Aging

Sirtuin 6 (SIRT6) is an enzyme that mice and we have that is associated with promoting a longer-than-average lifespan. Genetically removing SIRT6 from mice to cause SIRT6-deficiency shortens their lifespan. Therefore, Xu and colleagues used SIRT6-deficient mice to model premature aging. Interestingly, feeding young mice gut microbiota from these prematurely aged mice led to gray hairs and hypoglycemia — low blood sugar. Hypoglycemia is thought to be the main cause of death for SIRT6-deficient prematurely aged mice.

It’s been previously shown that a diet containing 35% vs. 16% fat increases the lifespan of rats. To determine if the anti-aging effects of a high-fat diet are mediated by changes in microbiota, prematurely aged mice were fed a high-fat diet composed of 16% carbohydrates, 19% protein, and 65% fat (mostly from coconut oil). This was compared to a standard diet of 64% carbohydrates, 19% protein, and 17% fat. The high-fat diet led to an over 80% increase in survival rate. The surviving mice also had higher glucose levels, indicating a reversal of hypoglycemia.

(Xu et al., 2023 | *Aging Cell*) **High-Fat Diet Increases Survival and Improves Blood Glucose.** Top: Prematurely aged mice fed a high-fat diet (HD) have an increased survival rate compared to mice on a standard diet (CD). Bottom: HD rescues blood glucose levels in prematurely aged mice (SIRT6 KO).

A family of gut bacteria called Enterobacteriaceae, which includes E. coli, increases in abundance with age in humans. Remarkably, Xu and colleagues found that prematurely aged mice have 300-fold higher levels of gut E. coli compared to healthy mice. Moreover, they found that pathogenic Enterobacteriaceae spread to the spleen, kidney, and liver of prematurely aged mice. However, feeding the prematurely aged mice a high-fat diet led to a reduction in gut E. coli and almost completely reversed Enterobacteriaceae levels in the visceral organs.

(Xu et al., 2023 | *Aging Cell*) **High-Fat Diet Reduces Pathogenic Bacteria in Visceral Organs.** Prematurely aged mice fed a normal diet (KOCD) have increased levels of pathogenic Enterobacteriaceae (Relative translocation to organs) in the spleen, kidney, and liver compared to normal mice fed a normal diet (WTCD) or high-fat diet (WTHD). However, Enterobacteriaceae levels are reversed by a high-fat diet (KOHD).

Our cells enter a senescent state when triggered by cellular stressors like DNA damage. Senescent cells reportedly accumulate with aging and contribute to age-associated organ deterioration and chronic inflammation. Prematurely aged mice exhibited increased markers of inflammation and senescence in the spleen, kidney, and liver. However, feeding prematurely-aged mice gut microbiota from high-fat diet-fed prematurely-aged mice reduced these markers.

(Xu et al., 2023 | *Aging Cell*) **High-Fat Diet Reduces Inflammation and Senescence.** Prematurely aged mice (SIRT6 KO) have increased inflammatory (TNFα, IL-1β, and IL-6) and senescence (p21 and p16) markers in the spleen, kidney, and liver. However, feeding prematurely gut microbiota from prematurely aged mice on a high-fat diet (KOHD-KO) reduces these markers.

The findings of Xu and colleagues suggest that the shortened lifespan of SIRT6-deficient mice is mediated by pathogenic gut bacteria that spread to the visceral organs and cause them to age faster by inducing tissue-degenerating inflammation and senescence. However, a high-fat diet alleviates this effect. The authors speculate that the high-fat diet could have anti-bacterial effects by increasing the level of bile salts to eliminate E. coli. Another explanation could be the use of coconut oil in the high-fat diet, which also has anti-bacterial effects.

Can Consuming More Healthy Fats in Moderation Counter Aging?

High-calorie diets often lead to weight gain. Since fats are calorically dense, it is easy to rake up the calories with high-fat foods. However, eating a high-fat diet without consuming excessive calories does not lead to weight gain. In fact, a high-fat diet, such as the ketogenic diet with low carbohydrates, can lead to weight loss. Additionally, some fats are beneficial, such as omega-3 fatty acids, known to have anti-aging effects on the brain. Thus, consuming more healthy fats (less saturated and trans fats) without going over the calories may be beneficial to the aging process.

“This study provides a rationale for the integration of microbiome-based high-fat diets into therapeutic interventions against aging-associated diseases,” state the authors.