Intermittent fasting: not an anti-aging remedy for mice

Publication in “Nature Communications”

Bonn/Munich (Germany), July, 31st, 2017. Fasting affects the body in a number of ways. Abundant evidence is available to show that it can even extend the lifespan of animals. But does fasting slow down the aging process? At least in mice, anti-aging effects are limited. This is the conclusion of a joint study by the German Center for Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München. However, the regular alternation of periods of food intake and fasting – a dietary regimen called “intermittent fasting” – slowed down the development of life-limiting cancers. As a result, the animals lived longer than mice with free access to food. 

In a laboratory study, Dr. Dan Ehninger and colleagues examined whether fasting slows down the aging process. Source: DZNE / Daniel Bayer

There is no doubt that fasting affects the body and the mind. While little research has been done into the long-term effects on humans, many studies have examined the consequences of life-long fasting in animals. These experiments have shown that mice placed on a strict diet live longer than controls with free access to food. Average lifespan is extended by around 15 percent in mice. In human terms, this would mean around 12 additional years of life. But do these animals age more slowly?

“Until now, this was the prevailing view within the scientific community. It is often based on the observation that fasting animals live longer than controls without restrictions in feeding. However, measuring only lifespan does not provide conclusive evidence regarding possible effects on aging. An extension in lifespan can be the result of an isolated effect on specific life-limiting diseases,” says Dr. Dan Ehninger, who leads a research group at the DZNE’s site in Bonn. “We therefore looked comprehensively at a large range of features associated with aging. Overall, we found only limited evidence for a retardation of aging as a consequence of fasting.”

 

Feeding every other day

In a joint effort, Ehninger’s team and researchers of the Helmholtz Zentrum München investigated the effects of “intermittent fasting”, i. e. regular feeding pauses, on mice: One group of rodents had unrestricted access to food and water. A second group was given unrestricted access to water, but was only fed on alternate days. This fasting plan started at the age of eight weeks and continued until the animals died a natural death. The study included 160 genetically identical male mice. The ones in the fasting group lived for 908 days on average, while those in the control group lived for 806 days.

All animals underwent extensive testing during their lives and after their deaths. These analyses encompassed more than 200 parameters, more than half of which change in the context of aging. Besides visual acuity, reflexes, and cardiovascular function, the scientists looked at a wide range of other traits including exploratory activity of the mice, immunological parameters, blood cell counts, and aging-associated histopathological changes in various tissues. “In conclusion, we found that both groups of mice aged in similar ways. Fasting had overall very little influence on this,” says Prof. Martin Hrabĕ de Angelis, head of the Institute of Experimental Genetics and the German Mouse Clinic at the Helmholtz Zentrum München.

Actually, the fasting mice did outperform controls on certain parameters: They were for example more active, and their blood contained higher levels of the oxygen transporter hemoglobin. However, in most cases, the researchers found similar improvements in a control group of young mice that had only fasted for four weeks, i.e. for a short period.

As these fasting effects manifested in young animals after a relatively short time, they cannot be explained by a delay in aging, says Ehninger. His conclusion: “Fasting had positive effects on the health of the mice but exerted hardly any influence on the dynamics of aging. Out of the 239 parameters we investigated, only seven featured a pattern consistent with a slowdown of aging. This applied for example to certain tissue changes in the brain and kidneys.”

 

Anti-tumor effect

Most of the mice died of cancer, irrespective of whether they had fasted or been fed a normal diet. “Cancers are known to be one of the most common natural causes of death in mice,” says Ehninger. “However, the tumors developed more slowly in the mice that fasted. This is why on average they lived longer.”

The anti-cancer effect of fasting in laboratory experiments is well documented. This phenomenon can be explained by the fact that periods of dietary restriction trigger metabolic changes. “As a result the organism is not set for growth. This metabolic brake can affect both healthy cells and cancerous ones. Accordingly, tumor development is suppressed,” says Hrabĕ de Angelis.

 

Similar calorie intake

The study also revealed that the fasting animals consumed almost the same amount of calories as those put on normal diet. “The mice adapted quickly to our experimental design and consumed more on a feeding day to compensate for the lack of food on the following fasting day,” says Ehninger. “Overall, calorie intake was reduced by only a few percent in fasting mice compared to controls. Nevertheless, they gained considerably less weight.” This is in line with results from other studies. “It shows that the effect of fasting is not necessarily due to caloric reduction per se but rather to metabolic changes caused by periods of fasting”, says Hrabĕ de Angelis.

“Intermittent fasting is currently a dietary trend. Experience shows that it can be an effective way to lose excess pounds. However, it must be emphasized that our results cannot be applied to a human context on a one-to-one basis,” says Ehninger. “But one can draw conclusions for future studies, for example, that a broad list of criteria must be taken into account when investigating aging processes. Aging is complex, it affects many organs and functions of our body. In this respect, our study provides many new insights for long-term studies on intermittent fasting in humans.”

Original publication
Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.
Kan Xie et al.
Nature Communications. DOI: dx.doi.org/10.1038/s41467-017-00178-3

Contact
Dr. Marcus Neitzert
DZNE, Communications
+49 (0) 228 / 43302-267
marcus.neitzert(at)dzne.de

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