Search PubMed⌕ Search

Biomedical subjects

R D Lipman

Publications and source records attributed to R D Lipman.

26 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

Age associated decrease of N-acetyl-beta-glucosaminidase activity in the lens epithelial cells from C57Bl/6 mice.

Lens epithelial cells were isolated from samples of C57BL/6 and CD-1 mice at different ages between 1 and 5 months, and assayed for the level of N-acetyl-beta-glucosaminidase and their ability to replicate in-vitro. The lens epithelial cells from C57BL/6 mice had a reduced replicative potential compared to other normal strains. A statistically significant decrease in active enzyme levels was demonstrated to be associated with increased animal age of C57BL/6 mice.

Acetylglucosaminidase↗