Other Free Encyclopedias » Medicine Encyclopedia » Aging Healthy - Part 1 » Cellular Aging: Basic Phenomena - Changes In Cell Morphology And Contact, Senescence And Cell-cycle Progression, Growth Signals And Senescence

Cellular Aging: Basic Phenomena - Cellular Senescence And Aging In Organisms

age physiological cells proliferative age mechanisms

Aging changes in organisms involve different kinds of cells and tissues and may result from multiple mechanisms. Thus, the aging of postmitotic cells, such as neurons, may proceed by a different set of mechanisms than that of proliferating tissues such as skin, the lining of the gut, or the blood-forming elements. Extracellular matrix macromolecules, such as collagen and elastin, also change with age, and presumably through mechanisms that are unique to them. There are also potentially profound effects resulting from interactions among these components during aging. Questions that have long been pondered by researchers studying proliferative senescence is whether the phenomenon occurs in vivo and whether it reflects changes that occur in organisms as they age. It is generally accepted that aging occurs at a cellular level. If this is true, then the mechanisms that control aging operate, and should be quantifiable, at a cellular level. But do the same mechanisms lead to cellular senescence? There is no simple answer to this question.

One of the strongest supports for the use of the cell-culture senescence model in studies of aging was the demonstration of a relationship between species' maximal life span and proliferative life span. There is also a donor-age-associated decline in mitotic activity and proliferation rates in a wide variety of human and rodent tissues in vivo. Both of these observations seem to suggest that the factors controlling the life span of intact organisms also control the growth characteristics and proliferative potential of cells in a culture environment. It has been observed that cells from patients with accelerated aging syndromes, such as Werner syndrome, have a reduced proliferative capacity compared with control cells from normal donors of the same ages. Additionally, this disease is associated with decreased mitotic activity, DNA synthesis, and cloning efficiency. Other types of diseases can also strongly modulate proliferative life expectancy. The effects of diabetes are particularly pronounced. All of these observations would appear to suggest that the physiological condition of the donor is reflected to some extent by the rate of cellular senescence observed in vitro.

On the other hand, studies by Robbins et al. (1970) were unable to identify any cells in the skin of older individuals with the phenotype that emerges in vitro. This raises the question of whether or not proliferative senescence actually occurs in the tissues of intact organisms? One of the strengths of the cell-culture model is that it has permitted the study of a single cell type; however, this can also be a limitation. Most studies of cell proliferation are unable to elucidate the relative contribution of intrinsic versus extrinsic factors. For example, do cells only senesce when separated from other types of cells and extracellular matrices, as in a culture environment? A group of studies bearing on this point involved the serial transplantation of normal somatic tissues to new, young, inbred hosts each time the recipient approached old age. In general, normal cells serially transplanted to inbred hosts exhibit a decline in proliferative capacity and probably cannot survive indefinitely. Additionally, it has been reported that proliferative capacity is diminished in spleen cells derived from old animals and transplanted into young irradiate hosts, and that mouse epidermis from old donors retain an age-associated increase in susceptibility to carcinogens regardless of whether they were transplanted into young or old recipients.

Cellular Aging: Basic Phenomena - Donor Age And Proliferative Life Span [next] [back] Cellular Aging: Basic Phenomena - The Genetics Of Cellular Senescence

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