Has Anyone Ever Died of Old Age?

The omission of aging as a legal cause of death and the largely unrecognized contribution the aging process plays in mortality is scrutinized

Senescence in vitro and ionising radiations—the human diploid fibroblast model

The influence of ionising radiations on ageing is still controversial. Since Hayflick established the concept that diploid cells have finite lifespan in vitro, human diploid fibroblast (HDF) cultures have been recognised as a potent experimental model for cytogerontological investigations. In this study HDF cultures in phase II were exposed to acute irradiation with either X-rays on fast neutrons. The replicative potentials and labelling indices with [3H]thymidine were measured post irradiation until the cultures ceased growth in phase III. Cell mortality was measured by cloning. The apparent loss in replicative potential of irradiated mass cultures was wholly attributable to the loss of viable clonogenic cells. The current concept of precocious clonal senescence in vitro as a late effect of irradiation in clonogenic survivors is not supported by the present experiments. Instead, our results suggest that exposure to a single dose of ionising radiations either causes total replicative incapacitation (killing) of HDF cells and their progeny early after irradiation or leaves their replicative potentials unperturbed

Aging in vitro and D-glucose uptake kinetics of diploid human fibroblasts

By use of a rapid technique, initial rates of D-glucose transport were obtained during the lifespan in vitro of a commercially available strain of human embryo lung fibroblasts (Flow 2000). The apparent Km of the D-glucose carrier did not change during senescence in vitro: = 1.8 mM (range 1.3-2.3) in phase II, = 1.8 mM (range 1.5-2.2) in phase III. Transport rates remained constant in stationary phase II cultures, which had completed between 30% and 80% of their replicative lifespan. A wide variation, however, was observed in terminally differentiated cells (phase III), which showed a two- to threefold increase in average cell size and protein content. In some senescent cultures, glucose transport calculated on a per cell basis was also two-to threefold increased, while it was strongly decreased (-75%) in others. When calculated per unit of cell water, protein, and surface area, respectively, transport rates in phase III cultures ranged from values established for stationary phase II cultures down to very low values. Detaching cells flushed off from senescent cultures did not show measurable rates of glucose transport into the inulin impermeable cell space. Present evidence argues against the idea that an impairment of D-glucose transport might precede loss of replicative potential in aging human fibroblasts. Instead our data indicate that the transport capacity of cell membrane finally decreases during postreplicative senescence in terminally differentiated cells

Formation of viable cell fragments by treatment with colchicine

Time-lapse cinematography of human fibroblasts revealed that mitotic cells separated into numerous cell fragments containing varying amounts of chromatin and cytoplasm when treated with colchicine. As cell fragments were very loosely attached to the surface of the culture vessel during their formation, they could be easily detached like mitotic cells by gently shaking the vessel and thus separated from normal interphase cells. Fragments obtained by this procedure were able to exclude trypan blue indicating, therefore, an intact cell membrane. When placed into Petri dishes many of them attached to and even spread out on the surface. Five hours later the majority of the attached fragments incorporated [3H]leucine. Time-lapse films showed that fragments were able to extend and retract pseudopodia at least for several hours after their formation. Although the fragments degenerated within a few days, in the present experiments the possibility was not excluded that fragments which had lost only a very small amount of chromatin and cytoplasm survived for longer periods of time. The observations clearly indicate viability of many newly formed fragments

Aging and Immortality in a Cell Proliferation Model

We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.Comment: 6 pages, 1 figure, 2-column revtex4 format; version 2: final published form; contains various improvements in response to referee comment