Infection of normal human diploid fibroblasts (HF) with the DNA tumor virus simian virus 40 (SV) leads to an extension of lifespan and concomitant increase in the levels of the viral large tumor antigen (T antigen) and the cellular protein p53. The intracellular localization of T antigen and p53 was mostly nuclear in both SVpre-crisis and SVpost-crisis cells, however certain population doubling (PD) of the SVpre-crisis cells exhibited some cytoplasmic staining. The DNA content of SVpre-crisis cells shifted to tetraploidy and the SVpost-crisis cells were near-tetraploid.
Table 1 summarizes the activities of hemopoietins on immature and mature basophils. IL-3, GM-CSF, and IL-5 enhanced basophil histamine release and in-vitro survival, while G-CSF, M-CSF, and IL-4 had no enhancing activities at all. In addition, IL-3 and GM-CSF induced basophil chemotaxis.
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.
We applied the Weibull distribution to the life-table and age-patterns of diseases in Japan. The life-table follows a composite Weibull distribution composed of initial failure and two stage wear-out failure periods. The extension of lifespan during the past century is manifested as increases in the scale parameters in all three periods and the shape parameters in the wear-out periods with female predominancy. The shape parameters of diseases show time-independent sex-dependent specific values.
Non-Hodgkin lymphoma is seen in approximately 5% of patients with AIDS. In recent years, the incidence has increased due to an extension of the average lifespan of HIV-infected individuals. In this article we describe the histological and clinical features of 45 patients with HIV-related non-Hodgkin lymphoma seen at the Academic Medical Centre between 1984 and 1991. There were 43 men and 2 women with a median age of 40 years. Most patients had high-grade B-cell lymphoma; 85% had extranodal sites. Prognosis was poor: overall median survival was only 3.8 months.
SV40 T-antigen-expressing human cells generally have an extension of lifespan until a period called "crisis" begins. On rare occasions a clone of cells emerges from the population in crisis and gives rise to an immortalized cell line. The present study compares the frequency of immortalization of cells from two different human lineages, lung fibroblasts and mammary epithelial cells.
Social scientists frequently refer to the 'greying' of the population in the west, the extension of the average lifespan to around the age of 76, and the projected increases in the numbers of people aged 85 and over, with the ensuing problems of chronic illness and disability that often accompany very old age. Increasing interest is being expressed in positive aspects of ageing: given the increases in life expectancy during this century, is it resulting in a life worth living?
Cellular senescence is a state of irreversible cell cycle arrest in which normal cells at the end of their lifespan fail to enter into DNA synthesis upon serum or growth factor stimulation. We examined whether proteins required for G1/S cell cycle progression were irreversibly down-regulated in senescent human fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells.
For several decades simian virus 40 (SV40) early region genes have been used as a means of generating immortalized human cell lines; however, the molecular mechanisms of this process have begun to be understood only recently. SV40-induced immortalization proceeds via two phases. In the first phase ("lifespan extension"), cells continue proliferating for a limited number of population doublings beyond the point at which normal cells undergo senescence.
We have examined the effects of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) on the growth, morphology, and lifespan of cultured human diploid fibroblasts. With human foreskin cells, HFF-1, and fetal lung cells, MRC-5, we have shown that carnosine at high concentrations (20-50 mM) in standard medium retards senescence and rejuvenates senescent cultures. These late-passage cultures preserve a nonsenescent morphology in the presence of carnosine, in comparison to the senescent morphology first described by Hayflick and Moorhead.