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R D Lipman

Publications and source records attributed to R D Lipman.

At least 19 recordsLinked to original sources
PubMed1996

Evidence that lysosomal storage of proteolipids is a cell autonomous process in the motor neuron degeneration (mnd) mouse, a model of neuronal ceroid lipofuscinosis.

The motor neuron degeneration (mnd) mouse has been documented to accumulate proteolipid and thus is a model of neuronal ceroid lipofuscinosis [Dunn, W.A., Raizada, M.K., Vogt, E.S. and Brown, E.A., Int. J. Dev. Neurosci., 12 (1994) 185-196; Faust, J.R., Rodman, J.S., Daniel, P.F., Dice, J.F. and Bronson, R.T., J. Biol. Chem., 269 (1994) 10150-10155]. While accumulation of proteolipid in the hippocampus of chimeric mice composed of mnd and +/+ cells was found to be proportional to the contribution of mnd in the brain, accumulation within individual cells was the same for cells from chimeric and age-matched mnd mice. Bone marrow transplantation was used to altering the milieu of circulating factors to determine whether this might modify the disease phenotype in mnd mice. Transplantation of bone marrow in neonatal or young mice did not reduce the age-associated accumulation of proteolipid within hippocampal neurons. The results of these experiments indicate that mnd results in a cell autonomous defect.

Aging↗
PubMed1996

Pathologic characterization of brown Norway, brown Norway x Fischer 344, and Fischer 344 x brown Norway rats with relation to age.

The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence functions as a biomaker of aging for all of the strains examined (p < or = .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 x BN F1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.

Aging↗
PubMed1996

Weight gain by middle-aged mice: dietary modification does not result in loss.

Dietary induced obesity susceptibility and persistence was examined in middle aged female retired C57BL/6J breeder mice. One year old mice were fed control chow (C), chow with added corn oil (O), or chow with added sweetened condensed milk (SCM) for 18 weeks, during which time food consumption and weight change were monitored. Mice in both the O and SCM groups gained significantly more weight than the C group. Weight increase correlated with caloric intake for the O and SCM groups. All mice were then fed standard laboratory chow for 22 weeks. The increased weight of both supplemented groups was maintained during this time suggesting that caloric intake is not the sole variable controlling weight maintenance in adult female mice. We encourage the use of older mice as a model to explore means of manipulating adult weight in humans.

Adipose Tissue↗
PubMed1995

Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer.

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.

Animals↗
PubMed1995

Is late-life caloric restriction beneficial?

Caloric restriction initiated in young mice and rats results in increases in mean and median life span. When caloric restriction is implemented in older animals, an increase in life span is still observed; however, the magnitude of the increase is not as great as that observed in animals calorie restricted since they were young. Here we report the results of a pilot study in which caloric restriction was initiated in mature, older rats. Survival rates and terminal pathology were characterized and compared between a cohort of 17 continually ad libitum fed Long Evans rats and a cohort of 18 Long Evans rats, which were gradually introduced to 33% restriction in diet consumption at 18 months of age. No difference in the median life span was observed between the two groups. The data suggest there may be a level of maturity, or a stage in the aging process, after which caloric restriction no longer increases longevity.

Aging↗
PubMed1995

Dietary restriction delays cataract and reduces ascorbate levels in Emory mice.

Dietary restriction can effectively extend lifespan and retard many age-related debilities. One hypothesis to explain the beneficial effects of dietary restriction is that it prolongs maintenance of cellular homeostasis by limiting endogenous oxidative stress and preserves oxidative defense mechanisms during aging. Ascorbate, a primary antioxidant, may play a major role in preventing oxidative damage. Ascorbate levels were determined in dietary restricted (R) and control (C) Emory mice, a strain which develops age-related cataract due in part to oxidative damage to lens proteins. Mice which consumed a diet restricted by 40% in calories had lower ascorbate concentrations in plasma, liver and kidney. Nevertheless, R animals showed significantly delayed progression of cataract which extended over the entire second half of life. The R diet did not result in different ascorbate levels in this lens. Aging was associated with a decrease in ascorbate in all the examined tissues except lens of both the R and C groups. It is not clear from these data that ascorbate is a prominent factor in the delay of cataract formation or other debilities in R Emory mice. However, it also appears unlikely that lens ascorbate is cataractogenic.

Aging↗
PubMed1993

Age-related gliosis in the white matter of mice.

A histopathologic study of the brains from 96 mice, ranging in age from 3 to 57 months in age, documents an age-associated increase in hypertrophic astrocytes in white matter. This report of gliosis is distinct from previously reported proliferation of glial cells in the grey matter. Four genotypes, CBA/HT6J, C57BL/6J, B6CBAT6F1J, and B6C3F1 were positive for this age-related lesion. Most very old mice utilized in this study were calorically restricted, a dietary manipulation long known to result in increased longevity in rodents. Caloric restriction appears to delay the age associated increase of this lesion. Immunoperoxidase staining for the astrocyte-specific glial fibrillary acidic protein (GFAP) confirmed the progressive increase in the density of stainable astrocytes with increase in age. GFAP staining of white matter increased in both diet groups with age. These findings present an interesting model for the study of aberrant cellular activity and perhaps neurodegeneration, modulated by caloric restriction.

Aging↗
PubMed1993

FRAR course on laboratory approaches to aging. The role of pathology in rodent experimental gerontology.

The distinction between aging and age-related disease is a blurred one at best. Pathologic lesions and diseases, while having obvious importance for the well-being of an individual, are not more indicative of aging than are silent or benign aging changes. All lesions are useful as biomarkers of aging. They are definable, and can be characterized in terms of their prevalence and severity in different species, genotypes, genders, and age groups. Some data from previous studies are presented as examples. Many lesions of aging are quite restricted, in terms of prevalence or severity, to specific genotypes, species or genders. Recognition of the very great diversity of lesion biomarkers between genotypes, genders and species should prevent investigators from extrapolating findings in one genotype-gender to any other.

Aging↗
PubMed1993

Husbandry factors and the prevalence of age-related amyloidosis in mice.

A retrospective study of the prevalence of amyloidosis in mice from several facilities was done. Amyloid deposition is an age-related lesion. The influence of common laboratory factors on the occurrence of this lesion was analyzed. This study documented genotypic difference in susceptibility to amyloidosis and showed that caging and pathogen status both impact on the number of cases of amyloidosis seen in a population. The lowest percentage of affected mice was seen when the animals were individually caged in a specific pathogen-free facility where conditions of stress were minimized.

Age Factors↗
PubMed1992

Mammary gland mass and breast cancer risk.

Evidence indicates that early life events and conditions, possibly extending to the intrauterine stages of life, and including energy restriction in early life, affect the risk of breast cancer. The mechanism of this effect is likely to be through a reduction in mammary gland mass and, inferentially, the total number of ductal stem cells. The evidence derives from epidemiologic and animal studies. It can explain certain epidemiologic findings that cannot be accounted for by more established breast cancer risk factors, including the more frequent occurrence of breast cancer in the left breast and the higher incidence of this disease among caucasian women than among Asian women in Asia.

Breast↗
PubMed1991

Calpain in cultured bovine lens epithelial cells.

Calcium dependent proteolysis was examined in supernatant prepared from cultured bovine lens epithelial (BLE) cells. The presence of the calcium activated protease, calpain, was indicated by immunorecognition of 80 kDa and 30 kDa subunits of calpain in BLE cell supernatant. Degradation of 125I-alpha-crystallin and FITC labeled casein by BLE cell supernatant were shown to be calcium dependent. Inhibition of activity was achieved with EGTA, calpastatin or CbzValPheH. The data presented are the first measurement of calpain activity in cultured lens cells.

Animals↗
PubMed1991

Reduction in rate of occurrence of age related lesions in dietary restricted laboratory mice.

This report describes the results of a study to find differences in the distribution of pathologic lesions between 40% dietary restricted (DR) and ad libitum (AL) fed mice of four genotypes, C57BL/6NNia, DBA/2NNia, B6D2F1NNia and B6C3F1NNia. Representative samples of all organs were studied from 1134 mice killed at 12, 18, 24 and 30 months of age. Approximately half were female, half male. All mice were fed a natural ingredient diet, NIH-31 and were maintained under pathogen free conditions. A total of 135 lesions was observed. The rate of occurrence of each of 35 common lesions is described for each age/genotype/sex in the study. Fifteen lesions are described in detail. Highly significant differences were found between mice of the same age, sex and genotype in the two diet groups in the percent rate of occurrence of total lesions, total tumors, and total lymphoid nodules of various organs. These parameters generally increased with age in both diet groups. For example, of female mice of all genotypes at 24 months, 51% AL and 13% DR mice had tumors. These percentages were 123% and 17% respectively at 30 months. The evidence presented here suggests that total tumors, total lymphoid nodules, total lesions, and absence of lesions are all useful measures of aging, independent of the life span, that reflect the long known effect of dietary restriction on reducing the rate of aging. These parameters, however, only partially reflected the longer life span of hybrid as compared with inbred mice.

Aging↗
PubMed1990

Aging and cellular maturation cause changes in ubiquitin-eye lens protein conjugates.

The eye lens is a useful tissue for studying phenomena related to aging since it can be separated into differentially aged or matured zones. This work establishes correlations between ubiquitin-lens protein conjugating capabilities and age, as well as the stage of maturation of bovine lens tissue. When exogenous 125I-ubiquitin was combined with supernatants of epithelial (least mature), cortex, and core (most mature) tissue, ATP-dependent conjugation of 125I-ubiquitin to lens proteins was most effective with the epithelial tissue preparation. Conjugate formation was greatest when lenses were obtained from young animals. Supernatants from cultured bovine lens epithelial (BLE) cells conjugated more 125I-ubiquitin to lens proteins than any tissue preparation. In all cases the predominant conjugates formed in these cell-free assays were of high molecular mass, although conjugates with masses in the 25-70 kDa range were also observed. Lens tissue and cultured BLE cell preparations were also probed with antibodies to ubiquitin to detect in vivo ubiquitin-lens protein conjugates. There was more free ubiquitin and ubiquitin conjugates in tissue from young as compared with older lenses. The greatest levels of conjugates were observed in cultured BLE cells. Specificity in the ubiquitination system is indicated since some of the conjugates formed in vivo appear identical to those formed in the cell-free assays and in reticulocytes using exogenous 125I-ubiquitin. Upon development and maturation of lens tissue (i.e., core as opposed to epithelium), there is accumulation of lower molecular mass conjugates.

Adenosine Triphosphate↗
PubMed1987

The in vitro replicative potential and cellular morphology of human lens epithelial cells derived from different aged donors.

Cultures of human lens epithelial cells have been established using explants of the lens capsule from different aged donors. Outgrowth from the explants occurs more quickly using material from younger as opposed to older donors. The total number of cells as well as the cumulative surface area covered by cell growth is more extensive with the explants from the lens capsules of younger donors as compared with the amount of cell growth from older donor lens capsules. Thus, there is an inverse correlation between donor age and the replicative capacity of human lens epithelial cells in vitro. The lens epithelial cell cultures from human donors of all ages have a finite replicative potential.

Adolescent↗
PubMed1982

Modification of the cataractous phenotype by somatic cell hybridization.

Characterized mouse lens epithelial cell cultures and their clonal isolates obtained from normal and cataractous mice display a finite life-span. The cells of cataractous origin have a decreased number of population doubling levels compared to the capacity of the normal cells to replicate in vitro. Hybrid cells derived from individual cell fusions of normal (CD-1, DBA/2) and cataractous (Catfr) lens epithelial cells have a mode of replication similar to that of normal cells. These results demonstrate that the abnormal in vitro replicative state of the cataractous cells has been modified by the addition of normal lens epithelial cell components.

Animals↗
PubMedDate not supplied

Pathobiology of aging rodents: inbred and hybrid models.

The definition of inbred strains of animals is provided, underscoring the homogeneity of the individuals in a strain, as well as the lack of allelic variation within each individual. Inbred animals present long-term reproducibility and relative stability, which facilitates experimentation over a long period of time. The derivations of several specific groups of inbred animals including coisogenic, congenic, and recombinant inbred lines are detailed. Applications for inbred strains to the study of aging including analysis of longevity characteristics, genes involved in the control of age-related parameters and gene interactions with other genes or the environment are presented. The concept of aging as a consequence of genes and the ramifications of competitive pleiotropy are discussed. The distinction between aging and age-related diseases or lesions is explored. Cumulative lesion incidence is suggested as a biomarker of aging.

Aging↗