Aging Aging

28 Cristofalo, Volker, and Allenskin fibroblasts with growth promoters can extend the proliferative life of culturesestablished from young donors but has negligible effects on cultures establishedfrom older donors (79). Aside from inherent species differences and theeffects of inbreeding that may influence these results, it is also apparent thatrodent skin is better protected from some types of environmental injury such aslight exposure. However, even in rodents, the relationship between donor ageand proliferative potential is not entirely clear. For example, an examination ofhamster skin fibroblast cultures established from the same donors at differentages reveals no age-associated changes in proliferative potential in animalsolder than 12 mo (78).To address these issues, we recently examined the proliferative potential of124 human fibroblast cell lines from the Baltimore Longitudinal Study of Aging(BLSA) (80). All of these cell lines were established from donors described ashealthy, at the time the biopsy was taken, using the criteria of the BLSA. Thisstudy revealed no significant change in proliferative potential of cell lines withdonor age, nor did we observe a significant difference between fetal and postnatallyderived cultures (80). Goldstein et al. (68) also reported that no relationshipbetween proliferative life-span and donor age could be found in healthydonors but did observe a relationship in diabetic donors. In addition, we performeda longitudinal study by determining the replicative life-span of celllines established from individuals sampled sequentially at different ages. As inthe case of the cross-sectional analysis, no relationship between donor age andreplicative potential was found in this longitudinal study. Indeed, cell linesestablished from individuals at older ages frequently exhibited a slightly greaterproliferative potential than the cell lines established from the same individualsat younger ages (80).1.2.1. Relationship of In Vitro and In Vivo ModelsOne of the underlying assumptions of in vitro aging models is that thechanges observed during proliferative senescence bear at least some homologyto those observed during aging in vivo. In fact, both similar (concordant) anddissimilar (discordant) changes have been observed between aging-associatedchanges observed in vivo and in vitro; these are summarized in Table 1.Although the results presented in Table 1 clearly demonstrate that somesimilarities do exist between aging in vivo and replicative senescence, itremains unclear whether these changes arise through a common mechanism orvia distinct pathways. As seen in Table 1, senescence in tissue culture andaging in the intact organism are not homologous. Others have noted that progressivemorphological changes begin to develop in diploid cell cultures shortlyafter they are established regardless of the donor age; no cells are found in vivo