Diet and the Suitability of the Male Fischer 344 Rat as a Model for Aging Research

Department of Physiology, University of Texas Health Science Center, San Antonio.
Journal of Gerontology 02/1993; 48(1):B27-32. DOI: 10.1093/geronj/48.1.B27
Source: PubMed


There has been concern about the suitability of the male Fischer 344 (F344) rat as a model for aging research because of the high prevalence of a single disease, severe nephropathy, at advanced ages which confounds the interpretation of an aging study. In a publication from our laboratory, Iwasaki et al. (1988) reported that replacing the casein in our standard semisynthetic diet with soy protein markedly decreases the progression of nephropathy with advancing age in ad libitum fed male F344 rats. In the present study, it is shown that replacing the casein with lactalbumin does not decrease the occurrence of severe nephropathy in ad libitum fed rats. It is also shown that dietary restriction (DR) studies can be effectively executed in the male F344 rat when soy protein is the source of dietary protein. It is further shown that when the energy intake of the rats fed soy protein-containing diets was reduced to 60% of the ad libitum intake, almost one-third of the rats died with an absence of severe morphologic lesions, that is, lesions which contribute to the death of the rat. It is concluded that the male F344 rat is an excellent model for aging research when soy protein is the source of dietary protein; no single disease process was found to be primarily responsible for death with such a diet.

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    • "For example, sarcopenia, left ventricular diastolic dysfunction, decline in heart rate variability, presbycusis, and neurodegeneration are prevented or delayed in DR rodents (Marzetti et al., 2009; Meyer et al., 2006; Mager et al., 2006; Someya et al., 2010; Martin et al., 2006). Additionally , data from postmortem pathological studies have shown that 30% of the DR rodents vs. 6% of fatter ad-libitum-fed animals die in old age free of pathological lesions (Shimokawa et al., 1993). Data from two ongoing primate studies show that 30% DR, started at a young age and sustained for 20 years, is safe and results in a more than a 50% reduction in cardiovascular and cancer morbidity and mortality (Colman et al., 2009; Mattison et al., 2012). "
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    ABSTRACT: Excess body weight and adiposity cause insulin resistance, inflammation, and numerous other alterations in metabolic and hormonal factors that promote atherosclerosis, tumorigenesis, neurodegeneration, and aging. Studies in both animals and humans have demonstrated a beneficial role of dietary restriction and leanness in promoting health and longevity. Epidemiological studies have found strong direct associations between increasing body mass index (BMI) and risks of developing type 2 diabetes, cardiovascular disease, and several types of cancer, beginning from BMI of 20–21 kg m−2. Although a recent meta-analysis suggests that overweight individuals have significantly lower overall mortality than normal-weight individuals, these data are likely to be an artifact produced by serious methodological problems, especially confounding by smoking, reverse causation due to existing chronic disease, and nonspecific loss of lean mass and function in the frail elderly. From a clinical and public health point of view, maintaining a healthy weight through diet and physical activity should remain the cornerstone in the prevention of chronic diseases and the promotion of healthy aging.
    Aging cell 03/2014; 13(3). DOI:10.1111/acel.12207 · 6.34 Impact Factor
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    • "Cause of death: As seen for breeding versus non-breeding semelparous animals and workers versus queens of social insects, AL and CR animals die from different causes (Shimokawa et al. 1993) (Fig. 4f). This is to be expected only if the two processes are fundamentally different rather than differing only in the speed at which they occur. "
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    ABSTRACT: Aging can be described as the accumulation of changes in organisms over time. Aging in organisms undergoing caloric restriction (CR) is widely considered as a slowed version of aging under ad libitum (AL) conditions. However, here we argue that aging under optimized CR is fundamentally different from aging under AL based on the following facts: (1) Comparing the two dietary groups, several age-related changes run in the opposite direction over time; (2) Switching from an AL to a CR diet clearly reverts (not only delays) several "normal" accumulated changes; (3) major causes of death are as different between both groups as they are between species. These observations support the idea that CR and AL initially modulate different metabolic and physiological programs, which exclusively over time generate two biologically different organisms. Such distinct diet-related senescence is analogous to the divergent aging processes and causes of death observed between castes of social insects, such as queens versus workers ("caste-related-senescence") and also between breeding versus non-breeding semelparous animals ("reproduction-related-senescence"). All these aging phenotypes are different not because they accumulate changes at a different rate, but because they accumulate different changes over time. Thus, the environment does not simply affect the individual aging rate through stochastic effects (e.g. U.V.) but also modulates the activation of a particular program/strategy that influences lifespan (e.g. caste, calorie intake). We refer to the environment-dependent aging patterns encoded by the genome as "senemorphism". Based on this idea we propose experimental schemes for aging, evolution and biomedical research.
    Biogerontology 05/2012; 13(4):457-66. DOI:10.1007/s10522-012-9383-6 · 3.29 Impact Factor
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    • "Whey protein was found to produce lower liver cholesterol concentrations in rats than casein [31]. Ageing studies in rats [32] [33] and mice [34] have also shown that casein as the primary source of dietary protein leads to a signi cant reduction in life expectancy when compared with soy protein, or whey. "
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    ABSTRACT: The consumption of cow's milk containing the g -casein variant A1 has been linked with type 1 diabetes (insulin-dependent diabetes mellitus; IDDM) in both NOD mice and BB rats. Supporting this, epidemiological studies that include both inter- and intra-country data yield a strong association of this protein's presence in milk with the incidence of IDDM. A stronger association can be observed when correlating g -casein A1 consumption with ischaemic heart disease (IHD) mortality, with a significant regression correlation coefficient (r2=0.86) . This suggests that the rate of g -casein A1 consumption, excluding that contained in cheese, is a more accurate predictor of heart disease between and within countries than that reported for traditional risk factors. It is often assumed that the response rates of illness to dietary inputs are dose specific. Should this not be the case, as animal studies of both IHD and IDDM indicate, then positive, null or negative outcomes will be achieved depending on the approach of the sample to a genetically at-risk group, or to the general population. In diseases such as those noted above where immune dysfunction or gut immune suppression appear to play a major role, failure to compare immune response may skew the data analysis and hide causality. Thus, the failure to detect strong associations between consumption of specific dietary components and diseases in studies of individuals, as is the case with both IHD and IDDM in the population at large, may reflect a non-linear relationship between dietary components and disease.
    Journal of Nutritional & Environmental Medicine 07/2009; 12(3):197-206. DOI:10.1080/1359084021000006858
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