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Rodents bred for alcohol preference live longer than rats bred for alcohol avoidance

15.01.2004


  • Researchers and clinicians know that drinking alcohol can have both beneficial and harmful effects.
  • Yet little is known about the effects of long-term, chronic alcohol consumption on survival.
  • A new study has found that rats bred to prefer alcohol are healthier and live longer than rats bred to avoid alcohol, whether they drink alcohol or not
  • Study authors ponder the implications of this unexpected yet significant finding.

Statistics clearly show that alcohol consumption can be detrimental to one’s health by increasing the chances of accidents, criminal activities, and health problems. However, little research has addressed the effects of long-term, chronic alcohol consumption on survival itself. A study in the January issue of Alcoholism: Clinical & Experimental Research uses rodents to do just that, and makes a surprising discovery: rats bred to prefer alcohol are healthier and live longer than rats bred to avoid alcohol, whether they drink alcohol or not.


"It is very difficult in human studies to separate the chronic effects of alcohol itself from the effects of factors that may accompany drinking," said David Sinclair, a senior researcher at Finland’s National Public Health Institute (KTL) and corresponding author for the study. "Factors such as smoking, stress and worry, nutritional problems, marital problems and difficulties in relations with others in general, etc. all produce effects of their own. Second, it is almost impossible in human studies to separate the effects of alcohol from the effects of those things that caused the drinking, including the genetic influences on alcohol consumption."

There are additional environmental factors that can complicate the interpretation of epidemiological data on the health effects of chronic alcohol consumption, said Petri Hyytiä, also a senior researcher at KTL. "First, it is very difficult to measure alcohol consumption accurately," he said. "In most cases, the estimates are based on self-reported intake, which usually tends to underestimate alcohol consumption. Second, drinking patterns may vary between individuals and different socio-economic groups in society."

Which is why using rodents that were bred for a specific alcohol response, in a controlled experimental setting, allows scientists to cut through many of these complicating factors.

"This is beautifully illustrated by the major finding in our study," said Sinclair, "that rats of the high-drinking AA line are healthier and live longer than rats of the low-drinking ANA line regardless of whether they drank alcohol or not. Since this was a controlled laboratory study with rats, we can conclude that the longevity effect was cause by genetics and that drinking did not have an effect on longevity. In human studies, the effects of genetics would be confounded by drinking, and the effects of drinking would be confounded by the genetics that make the person drink more."

For this study, researchers examined two groups of rats: 194 (96 male, 98 female) alcohol-preferring rats (Alko, alcohol or AA) and 123 (62 males, 61 females) alcohol-avoiding rats (Alko, non-alcohol or ANA). Some of the AA rats (104 AA, 66 ANA) were given 12 percent alcohol as their sole source of fluid from three to 24 months of age. The remaining ANA rats received water. All rats that died during the experiment, as well as those killed at 24 months of age, were autopsied and pathological findings were recorded.

"There were two major findings," said Sinclair, "one negative and one positive, but both rather unexpected. First the negative: a lifetime of forced high-alcohol consumption in rats did not shorten their lives. This was true regardless of whether the rats were of the AA or ANA line and regardless of their gender. The positive finding was that the AA rats were healthier and lived much longer than the ANA rats; for example, the death rate among the ANA rats was three times higher than among the AA rats. This was true regardless of whether they had a lifetime of high alcohol consumption, or were maintained without alcohol. In other words, the genes that were selected when producing the high-drinking rats had other properties that made these animals healthier and live longer. Or the genes we got when producing the alcohol-avoiding rats had other characteristics that were damaging to their health. Or both."

Sinclair cautioned against interpreting these findings as proof that alcohol consumption is harm-free. "As difficult as human studies in the area are, they still give strong evidence that chronic intake of large amounts of alcohol is detrimental," he said.

Hyytiä concurred. "When we compare this study with human epidemiological data, we have to keep the important limitations of the rat model in mind," he said. "First, rats have a higher metabolic capacity than humans. This means that even if rats drink alcohol as their only source of fluid, they are able to metabolize alcohol so efficiently that they have measurable amounts of alcohol in their blood only a few times during the day. Therefore, it may not be surprising that alcohol per se did not have harmful health effects."

Sinclair said the latter or ’positive’ finding raises some intriguing questions that provide direction for future research.

"It is now clear that there are rather widespread genes in the human population that increase the risk of developing alcoholism, and there are others – such as the one causing some Orientals to flush when they drink – that provide protection from alcoholism," he said. "This is a well-known fact. It also is a paradox. It seems very likely that developing alcoholism is a very detrimental trait from an evolutionary point of view. Children born to parents who are alcoholics should have been less likely to survive and reproduce. Tribes in which many of the elders have developed alcoholism should have been less adept at raising children who survive and reproduce. If this is true, why hasn’t evolution removed those genes promoting the risk of alcohol, and conversely, why haven’t the ’flusher’ genes become universal in Oriental populations? Could our discovery – that rats with genes promoting drinking live longer than ones with genes suppressing drinking – be related to this paradox in humans? These are extremely important questions that merit further investigation."


Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper included: Maija Sarviharju and Kalervo Kiianmaa of the Department of Mental Health and Alcohol Research at the National Public Health Institute; Jarno Riikonen and Antti Hervonen of the Tampere School of Public Health at the University of Tampere; and Pia Jaatinen of the Department of Internal Medicine at Tampere University Hospital, and of the Medical School at the University of Tampere; all in Finland. The study was funded by the Medical Research Fund of Tampere University Hospital, and the Finnish Foundation for Alcohol Studies.

David Sinclair, Ph.D. | EurekAlert!
Further information:
http://www.alcoholism-cer.com/

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