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Ultraviolet light-induced DNA repair synthesis in hepatocytes from species of differing longevities.

The DNA repair capabilities of cultured hepatocytes derived from five mammalian species in response to a broad range of ultraviolet light exposures were measured. Differences in the induction of DNA repair synthesis and the proportion of responding cells were noted only for the lowest fluences. These differences appeared to be positively correlated with the potential lifespans of the species involved; mouse and rat hepatocytes displayed less repair than those from guinea pig or rabbit. At higher fluence levels, however, there were no differences in the amount of repair induced. Thus the maximal repair potential of hepatocytes derived from the rat, mouse, hamster, guinea pig and rabbit were the same.

Animals↗

Relationship between antioxidant defenses and longevity in different mammalian species.

The general objective of this investigation was to examine the relationship between oxygen free radicals and the aging process. Comparisons of antioxidant defenses were made in six different mammalian species, namely, mouse, rat, guinea pig, rabbit, pig and cow, which range from 3.5 to 30 years in their maximum life span potential (MLSP). Activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase, and concentration of glutathione were measured in the liver, the heart, and the brain. SOD and catalase activities were positively correlated whereas glutathione concentration was negatively correlated with MLSP. Glutathione peroxidase activity exhibited a variable pattern: being positively correlated with MLSP in the brain and negatively correlated in the liver and the heart. In each organ, MLSP was correlated with relatively high levels of one or two of the above antioxidants and low levels of the other antioxidants, indicating the possibility of a compensatory balance among various components of the antioxidant system. No obvious pattern of a relationship was detectable between the overall level of antioxidant defenses and MLSP among the mammalian species examined. The implications of this finding concerning the role of oxidative stress in the aging process and the free radical hypothesis of aging are discussed.

Aging↗

Evolution of longevity in mammals.

Maximum life span is a characteristic of each species, and a diversity of maximum species life spans is seen in each mammalian order. It is argued here that different clusters of related long-lived species evolved independently. A variety of genes could have been involved such as genes for somatic maintenance and genes for resistance to causes of death, including fatal diseases. There are explanations based on natural selection for the long maximum human life span, half of which is post-reproductive.

Animals↗

Induction and repair of benzo[a]pyrene-DNA adducts in C57BL/6 and BALB/c mice: association with aging and longevity.

In this study, we employed the sensitive 32P-postlabeling assay to assess the influence of age on the formation and disappearance of benzo[a]pyrene (B[a]P) DNA adducts in six organs of two different mouse strains with different life spans, C57BL/6ByJ (C57BL/6) and BALB/cByJ (BALB/c). Following a single, intraperitoneal treatment with 50 mg B[a]P per kg of bodyweight, maximum formation of the major B[a]P-derived adduct, trans-(7R)-N2-[10-(7 beta,8 alpha, 9 alpha-trihydroxy- 7,8,9,10)-tetrahydrobenzo[a]pyrene]-yl-deoxyguanosine (BPDE-N2-dG), appeared to be age- and organ-dependent; minor differences were observed for the same organs between the two mouse strains. The maximum formation of BPDE-N2-dG in the various organs from young and old mice differed by a factor of 2-4 and was two- to eightfold lower in organs from old mice as compared to young mice. The removal of BPDE-N2-dG, up to 7 days after the treatment, was apparently age- and strain-dependent; non-significant differences were observed for organs within strains at each age studied. In young C57BL/6 mice, which have a greater life expectancy than BALB/c, the rate of disappearance of BPDE-N2-dG was significantly higher in liver and heart as compared to young BALB/c. At the older age a decrease in the rate of BPDE-N2-dG disappearance was observed more frequently, and to a relatively greater extent, in organs from C57BL/6 mice as compared to BALB/c mice. These results are discussed in relation to the differences in life spans and the incidence of pathological lesions between the two strains of mice.

Aging↗

The limit to human longevity: an approach through a stress theory of ageing.

Survival to old age is enhanced by high vitality and resilience associated with substantial physiological and morphological homeostasis. This is underlain by genes for stress resistance, which confer high metabolic efficiency and hence adaptation to the energy costs of the stresses to which free-living populations are exposed. Under the stress theory of ageing, selection for genes for stress resistance is primary, and achieved life-span is secondary. In some human populations of the modern era, selection for stress resistance is less intense than in earlier times, because of adequate nutrition and reduced exposure to environmental stresses. Such relaxed selection should permit the accumulation of deleterious mutants that are likely to be stress sensitive. Accordingly, increased maximum life-span in future human populations would appear difficult to achieve.

Adaptation, Physiological↗

The effect of reduced physical activity on longevity of mice.

Reduced physical activity leads, in female mice, to a reduction of the average and maximal life span. The average age at death of the inactive experimental group was 497 +/- 121 days (mean +/- S.D.) compared to 557 +/- 139 days in the active control group, and the six oldest inactive experimental mice died at age 732 +/- 50 days, while the six oldest active control mice died at 890 +/- 52 days. The restriction of mobility was connected with a higher growth rate and a higher body weight in spite of a significant decrease in food intake. In spite of a reduced food intake leading to a reduced whole body metabolism, the results show that mobility restriction shortens life span in female mice.

Analysis of Variance↗

Longevity and selenium deficiency: evidence from the People's Republic of China.

Data were abstracted from the Atlas of Aged Population in the People's Republic of China and from The Atlas of Endemic Diseases and their Environments in the People's Republic of China. The spatial distribution of the elderly, those aged 80 years or more in 1982, in 2408 counties, was then compared with the prevalences of Kaschin-Beck and Keshan diseases, both of which involve extreme selenium deficiency. Pearson chi-square, the Mantel-Haenszel test for linear, association and Spearman correlation all clearly indicate that the elderly in China are not normally distributed. Far fewer people of advanced age reside in those counties in which Kaschin-Beck and Keshan diseases are endemic than in unaffected counties. The possible reasons for this are thought to include elevated mortality from endemic and chronic diseases in selenium deficient areas and accelerated ageing due to excessive cellular damage caused by free radicals. These two phenomena may be related.

Age Distribution↗

Biocultural risks in longevity: Samoans in California.

Because migration is such a widespread phenomenon, studies of the effects of accompanying life change on the health and well-being of the migrant have special significance in areas like California that support large migrant communities. Previous studies have shown that increased weight and elevated blood pressure may be linked to changes in diet, exercise habits, and the altered sociocultural milieu of the migrant. Among Samoans, a Pacific Island population of Polynesian descent, these changes appear to be particularly prominent in segments of the population that have moved to the environment of Hawaii, which epidemiologic studies have characterized as "intermediate-modern.' Preliminary findings from a survey of weight, height, blood pressure, fasting glucose levels, and mortality records among Samoans living in California indicate that individuals living under more highly urbanized conditions exhibit even more pronounced changes. Adult weight among Samoans in California (San Francisco) greatly exceeds that of their counterparts in Hawaii and Samoa. Elevated blood pressures are also seen, though the extent to which this is associated with excessive weight gain is unclear. The number of individuals with high (greater than or equal to 160 mg/dl) fasting plasma glucose levels would be consistent with a population in which the prevalence of diabetes is many times higher than in the U.S. population. Although mortality patterns are difficult to determine for this population, available records suggest an excess mortality from cardiovascular diseases of all types among adult Samoans under age 50. Further investigations will attempt to link biobehavioral changes in the migrants' lifestyle to these observed patterns of risk.

Adult↗

Relationship of body-weight gain to longevity and to risk of development of nephropathy and neoplasia in Sprague-Dawley rats.

The relationship of weight gain to survival, risk of development of chronic progressive nephropathy and risk of development of various neoplasms has been studied in the control groups from two routine chronic toxicity studies in Sprague-Dawley rats. The groups comprised 100 CFY strain rats of each sex observed up to the age of 109 wk and 120 CD strain rats of each sex observed up to 111 wk of age (females) or 121 wk (males). The eventual incidence of tumours was found to be related to body weight at several ages. There was also a statistically significant association between high body weight at various ages and increased mortality, particularly in the CD strain and particularly in females. The 'heavy' rats proved to have an increased risk of developing both progressive nephropathy and certain tumours. This relationship was particularly marked for pituitary tumours in both sexes and for benign and malignant mammary tumours in females, and was significant irrespective of whether tumours coexisting with marked or severe progressive nephropathy were classified as fatal or incidental. There was also some evidence that increased body weight was positively associated with risk of islet-cell tumours and lipomatous tumours in males and fibromatous tumours in females. The observations illustrate how non-specific factors, such as those that affect body weight, may profoundly influence mortality and tumour incidence in chronic toxicity studies. The findings also highlight the difficulty of classifying particular neoplasms as incidental or fatal where other potentially life-threatening pathology (e.g. progressive nephropathy) is present.

Adenocarcinoma↗

The Biosure Study: influence of composition of diet and food consumption on longevity, degenerative diseases and neoplasia in Wistar rats studied for up to 30 months post weaning.

The 1200-rat Biosure Study had six interrelated aims: (1) To see whether dietary restriction (80% ad lib.) reduces the age-standardized incidence of fatal or potentially fatal neoplasia before the age of 30 months. (2) To see whether the beneficial effects of diet restriction can be achieved by (a) limiting the daily period of access to food to 6 hr, or by (b) limiting the energy value of the diet. (3) To see whether reduced calorie intake between weaning and age 4 months influences survival and/or incidence of non-neoplastic and neoplastic diseases. (4) To compare effects of food consumption, energy intake and protein intake on survival and disease. (5) To study the relationships between body weight at different ages with eventual survival and disease incidence. (6) To provide a database for studying relationships between various in-life measurements and eventual survival and disease incidence in individual animals. Twelve groups of SKF Wistar rats consisting of 50 animals of each sex were fed according to different dietary regimens from when they were weaned at the age of 3 wk until they died, or had to be killed because they were sick, or until the experiment was terminated at 30 months. For five of the 12 dietary regimens, satellite groups consisting of 30 animals per sex were maintained in parallel and used to supply information on the effect of diet on circulating hormone levels during the course of the study. During the 13 wk post weaning a Standard Breeder diet (SB) was provided either ad lib. (four groups), 80% ad lib. (three groups), or with access to food limited to 6 hr per day (one group). During this same period two other groups were fed a Low Nutrient Breeder diet (LB) ad lib. A further group was fed a Low Nutrient Maintenance (high fibre) diet (LM) ad lib. Finally, one group was fed the high protein Porton Rat diet (PR) ad lib.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Long-term feeding studies in mice fed a diet containing irradiated fish. I. Multigeneration reproduction, mutagenicity, teratology, and longevity studies.

A wholesomeness feeding study was carried out in mice fed equal amounts of cod or redfish, comprising 45% of the diet. Three groups of animals received either irradiated [1.75 kGy (175 krad)] fish, non-irradiated fish or stock ration. A 90-day subchronic study, a multigeneration reproduction, a dominant lethality and a teratology study were carried out together with an 80-week oncogenic study on the F1 generation. No adverse effects were noted on growth, reproduction and litter behaviour, in relation to dominant lethality, teratogenicity or oncogenicity.

Animals↗