Various concentrations of oxygen were used to determine the optimum culture medium PO2 for survival and proliferation of attached human and mouse fibroblasts grown from different inoculum sizes. When T-15 flasks were seeded with less than or equal to 2 X 10(4) cells (less than or equal to 1.3 X 10(3) cells/cm2), the highest plating efficiencies and cell yields were obtained with a culture medium PO2 of 40-60 mm Hg.
An extension of the mathematical model of immunological tolerance including two categories of B and T helper cells, each having a different lifespan, is presented. The simulated recovery from tolerance is compared with experimental data on B and T helper cell tolerance to human gamma globulin (HGG) induced in adult mice. The performed simulation runs suggest the conclusion that in this case it seems impossible to incorporate a high ratio of both, long-lived B cells and/or short-lived T helper cells, if good agreement with the available experimental data should be preserved.
Tumor-promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses.
Lymphocytes have a finite and predictable proliferative life span in culture similar to that observed in fibroblasts. In general, the senescence of human fibroblasts is inevitable and irreversible, but their proliferative life span can be extended by certain DNA tumor virus oncogenes, such as the large T antigen of the SV40 virus. Here, we show that human T lymphocytes (HTL) can be stably transfected with SV40 large T and that expression of T antigen extended the life span of T cell cultures.
Reactive oxygen (RO) has been identified as an important effector in ageing and lifespan determination. The specific cell types, however, in which oxidative damage acts to limit lifespan of the whole organism have not been explicitly identified. The association between mutations in the gene encoding the oxygen radical metabolizing enzyme CuZn superoxide dismutase (SOD1) and loss of motorneurons in the brain and spinal cord that occurs in the life-shortening paralytic disease, Familial Amyotrophic Lateral Sclerosis (FALS; ref.
Accessible and readily utilized software, tables and approximation formulae have been developed to estimate power and sample size for studies of time to event (survival times) when the survival times are assumed to be exponential. These methods can markedly misestimate power when the distribution is Weibull and not exponential. The Weibull distribution with increasing hazard is common in aging research, especially when the whole life span of the subjects is of interest.
SV40 infection of human cells results in both transformation and lytic infection. We have used origin-defective viral mutants which are unable to replicate in permissive cells to help analysis of transformation. Expression of large T antigen (T ag) and small t antigen results in the altered growth phenotypes characteristic of transformation in other species. Human diploid fibroblasts (HF) have a limited lifespan and undergo senescence; T ag results in extension of lifespan but only in rare cases are the cells capable of continuous growth and are immortal.
The biology of telomeres and telomerase has been the subject of intensive investigative effort since it became evident that they play a significant role in two important biological processes, the loss of cellular replicative capacity inherent to organismal ageing and the unrestricted cell proliferation characteristic of carcinogenesis. Telomere shortening in normal cells is a result of DNA replication events, and reduction beyond a critical length is a signal for cellular senescence.
Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
The question of whether aging - the process that converts fit adults into frailer adults with a progressively increased risk of illness, injury, and death - is under genetic control is ambiguous, and its answer depends on what one means by aging. Natural selection can select for genes that retard aging, but only in species and niches where the value of prolonged survival outweighs its costs. Although the form aging takes can be affected by variations at many genetic loci the number of loci that moderate the pace of synchronized decay may be far smaller.