Cellular Aging: Basic Phenomena
Senescence And Differentiation
Although most of the studies of cellular senescence have focused on similarities to aging, some have considered homologies with developmental processes. A commonly held view is that cellular aging may follow a differentiation lineage model. In fact, it has been suggested that the finite life span of cells may represent a differentiation of cell types, and that the process of diploid cell growth may have an in vivo counterpart in hyperplastic processes (uncontrolled proliferation). Chronological time appears to be significantly less important than division events in the progression of the phenomenon. Although the state of differentiation may change in cells that senesce in vitro, there is, in fact, no evidence that the changes in gene expression observed in fetal cells as they senesce, in vitro, are tantamount to differentiation, in vivo. While analogous changes can be found, they are greatly outnumbered by the dissimilar features that characterize these two distinct phenomena. Hence, a comparison of senescence-associated changes and differences that exist between fetal and postnatal cells reveals little similarity.
At least some analogous similarities exist between senescence in fetal fibroblasts and developmental changes that occur in vivo. For example, it has been observed that addition of platelet-derived growth factor-BB (PDGF-BB) stimulates an increased mRNA abundance of the transcript encoding PDGF-A chain in fetal and newborns and a relatively small response in adult cells. Senescence in vitro of newborn fibroblasts appears to result in the acquisition of the adult phenotype by decreasing their response to PDGF-BB. On the other hand, there are a number of differences reported between cell lines established from fetal and adult tissues that are related to growth factor requirements for proliferation and migration that remain disparate, even as these cultures become senescent. For example, fetal dermal fibroblasts will proliferate in either plasma or serum, while adult dermal fibroblasts require serum. It is also noteworthy that the expression of some genes, such as SOD-2, increases during proliferative senescence but only in some types of fibroblasts; in other types of fibroblasts no change is observed (see Allen, et al., 1999). It might be expected that cells placed in culture will be deprived of those signals that direct the normal sequence of developmental pathways, and that differentiation, if it occurs, is to an aberrant state. Alternatively, fetal cell lines may arise from different precursor cells than adult fibroblasts, and thus merely differentiate to a different fibroblast type. What is apparent from studies of senescence is that similarities as well as discrepancies are observed when it is compared to either aging or development. As a result of this, the model is obviously less useful for predicting aging or development changes in vivo than it is for studying known changes in an isolated cell system.
VINCENT J. CRISTOFALO R. G. ALLEN
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