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Print version ISSN 0102-6720
ABCD, arq. bras. cir. dig. vol.25 no.1 São Paulo Jan./Mar. 2012
Nelson Adami Andreollo; Elisvânia Freitas dos Santos; Marina Rachel Araújo; Luiz Roberto Lopes
Laboratory of Enzimology and Experimental Carcinogenesis, Faculty of Medical Sciences, State University of Campinas - UNICAMP, Campinas, SP, Brazil
Millions of mice are used annually in research and teaching. The exact relationship
between age of the animals compared with the age of humans is still subject to
discussion and controversy.
OBJECTIVE: Literature review analyzing the age of rats in comparison with men age.
METHODS: Were reviewed the existing publications on the subject contained in Medline / Pubmed, Scielo, The Cochrane Database of Systematic Reviews and Lilacs crossing the headings rats, experimental surgery and physiology.
RESULTS: Rats rapidly develop during childhood and become sexually mature at about six weeks old, but reach social maturity five to six months later. In adulthood, every month of the animal is approximately equivalent to 2.5 human years. Several authors performed experimental studies in rats and estimated 30 days of human life for every day life of the animal.
CONCLUSION: The differences in anatomy, physiology, development and biological phenomena must be taken into consideration when analyzing the results of any research in rats when age is a crucial factor. Special care is necessary to be taken when the intention is to produce correlation with human life. For this, special attention is needed to verify the phase in days of the animal and its correlation with age in years of humans
Headings: Rats. Experimental surgery. Physiology.
Currently is difficult to evaluate the number of animals employed in scientific experiments or in teaching. An estimation suggests some dozens of millions for year, being 15 millions in the United States, 11 millions in Europe, five millions in Japan, two millions in Canada and less than one million in Australia. In Brazil, the number is unknown, but insignificant in comparison with the world totals. It can be said that 80% of the experimental animals are rodents - mice, rats and guinea pigs -, and that others 10% are fish, amphibians, reptiles and birds. A third group includes rabbits, goats, bulls, pigs and in smaller amount, dogs, cats and some species of primates. They substitute the human being as experimentation object in scientific researches, in the preparation and quality control of medicines and in teaching1.
Fagundes and Taha3 looked for database information in Medline (National Library of Medicine-USA), Lilacs (Latin-American Literature and of Caribbean in Sciences of the Health), Scielo (Scientific Eletronic Library Online) and Library Cochrane (The Cochrane Database of Systematic Reviews) about the six animals species more commonly mentioned, in a period of four years. This survey showed that the rats were the animals more used in research, followed by mouse, rabbit, dog, pig and primate. About 85% of the articles in Medline and 70,5% of the articles in Lilacs employed rats and mice.
Many questions often arise when animals are being used as models of human diseases and biology: When are these animals considered aged? Which is the relationship of the age of the rat with the human age? How many rat days are equal to one human year? The number of existing publications and focusing on the issue in depth is very limited.
The objective of this review is to evaluate these issues on the existing literature.
Were reviewed the existing publications on the subject contained in Medline / Pubmed, Scielo, The Cochrane Database of Systematic Reviews and Lilacs crossing the headings rats, experimental surgery and physiology.
The R. norvegicus and the black rat (R. rattus) belong to the murine family (the same that originated the mice and hamsters) and came from Asia to America and Europe traveling with humans. Today there are 51 known species of the Rattus. Norway rats originated in the Asia, probably in northern China and Mongolia are wild living rats. The albino rats were used in laboratories for physiology studies in the early 19th century, and the white rats were brought from Europe to America from 1856. The Wistar rats were created by Helen Dean King, Philadelphia (USA) in 1909. Currently Wistar rats and Sprague-Dawley rats are gradually becoming the most used worldwide in laboratory5,8,13.
Compared to humans, rats have a brief and accelerated childhood. Rats develop rapidly during infancy and become sexually mature at about six weeks of age. Humans, on the other hand, develop slowly and don't hit puberty until about age 12 to 13 years (8 to 16). Social maturity is obtained in five to six months of age. In adulthood, each rat month is roughly equivalent to 2.5 human years. Female rats enter menopause between ages 15 and 18 months, while humans between 48 and 55 years11.
Domestic rats live about two to 3.5 years11. In agreement with Quinn the average laboratory rat lives approximately three years10. In a survey, rat lifespan in the UK was 21.6 months, and 95% percent had died by age of three years. In contrast, 95% of rats living wildly tend to live less than one year11.
The worldwide human life expectancy is about 70 years, with differences among countries. Human lifespan tends to correlate with economic development. Quinn estimates that humans can live approximately 80 years10. Table 1 tries to estimate the relative age of the rat in relationship to the human.
Several authors accomplished experimental studies in rats and they demonstrated a correspondence of 30 days of the man's life to every day of life of the rat4,6,7,9.
Quinn10 mentioned that there is no simple answer on making age comparisons between humans and animals. So, considering all the analysis and using the birth as a starting point for both species, the conversion rate in shown in Figure 1.
The most important concept is that the results are different depending on how old are rat/man and what factors are being analyzed. If you are making comparisons in the very early stages of life, will be drastically different compared with adulthood4,6,7,9,10. For example, if you are using an obese rat model to study neurobiological changes associated with bariatric surgery and you are looking at changes in 10 to 12 week old animals, a conversion rate of approximately 10 to 12 rat days per human year would probably be appropriate12. In contrast, if you are studying mammary gland developmental changes in association with diet and you are looking at gland development from three to seven week of age, then a conversion of approximately four rat days per human year would probably be more relevant2.
Rats and animal models in research in general can be very important and useful. The results can be applied to humans with precaution. They can not be interpreted as miniature people. Just because the rat's lifespan is three years does not mean it lives a miniature human lifetime within those three years8,9,10,11.
The differences in anatomy, physiology, development and biological phenomena must be taken into consideration when analyzing the results of any research in rats when age is a crucial factor. Special care is necessary to be taken when the intention is to produce correlation with human life. For this, special attention is needed to verify the phase in days of the animal and its correlation with age in years of humans.
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2. Eason RR, Velarde MC, Chatman Jr, L Till SR, Geng Y, Ferguson M. Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development, J Nutr. 2004; 134: 3370-7. [ Links ]
3. Fagundes DJ, Taha MO. Animal disease model: choice´s criteria and current animals specimens. Acta Cir Bras. 2004; 19(1):59-65. [ Links ]
4. Gittes RF. Carcinogenesis in ureterosigmoidostomy. Urol Clin North Am. 1986;13(2):201-05. [ Links ]
5. Hayward BE, Zavanelli M, Furano AV. Recombination creates novel L1 (LINE-1) elements in Rattus norvergicus. Genetics. 1997;146(2):641-54. [ Links ]
6. Iandoli Júnior D, Nigro AJT, Sementilli A, JulianoY, Novo NF. End-to-end esophagogastric anastomosis comparative study, between a single layer and submucosa-mucosa invagination technics: in rats. Acta Cir Bras. 2000; 15(1): 14-22. [ Links ]
7. Klee LW, Hoover DM, Mitchell ME, Rink RC. Long term effects of gastrocystoplasty in rats. J Urol. 1990;144(5):1283-7. [ Links ]
8. Krinke GJ, Kaufmann W, Mahrous AT, Schaetti P. Morphologic characterization of spontaneous nervous system tumors in mice and rats. Toxicol Pathol. 2000;28(1):178-92. [ Links ]
9. Peckham JC. Experimental oncology. In: Baker HJ, Lindsey JR, Weisbroth SH. The laboratory rat. New York: Academic Press;1979; p.119. [ Links ]
10. Quinn R. Comparing rat's to human's age: How old is my rat in people years? Nutrition. 2005; 21:775-7. [ Links ]
12. Romanova IV, Ramos EJ, Xu Y, Quin R, Chen C, George ZM. Neurobiological changes in the hypothalamus associated with weight loss after gastric bypass. J Am Coll Surg. 2004; 199:887-95. [ Links ]
13. Verneau O, Catzeflis F, Furano AV. Determination of the evolutionary relationships in Rattus sensu lato (Rodentia:Muridae) using L1 (LINE-1) amplification events. J Mol Evol. 1997;45(4):424-36. [ Links ]
source: none From
the Laboratory of Enzimology and Experimental Carcinogenesis, Faculty of Medical
Sciences, State University of Campinas - UNICAMP, Campinas, SP, Brazil
Nelson Adami Andreollo
Conflicts of interest: none
From the Laboratory of Enzimology and Experimental Carcinogenesis, Faculty of Medical Sciences, State University of Campinas - UNICAMP, Campinas, SP, Brazil