Comparative cellular biogerontology: primer and prospectus

Abstract

Most prior work on the biological basis of aging has focused on describing differences between young and old individuals but provided only limited insight into the mechanisms controlling the rate of aging. Natural selection has produced a goldmine of experimental material, in the form of species of differing aging rate, whose longevity can vary by 10-fold or more within mammalian orders, but these resources remain largely unexplored at the cellular level. In this review article we focus on one approach to comparative biogerontology: the strategy of evaluating the properties of cultured cells from organisms of varying lifespan and aging rate. In addition, we discuss problems associated with the analysis and interpretations of interspecific variation of cellular trait data among species with disparate longevity. Given the impressive array of 'natural experiments' in aging rate, overcoming the technical and conceptual obstacles confronting research in comparative cellular gerontology will be well worth the effort.

Figure 1

Bird fibroblasts are more resistant to lethal stress than mouse or rat fibroblasts derived from wild-caught animals. Note the lack of overlap between values for bird cells and mean levels for mouse and rat cells. Values shown are LD₅₀’s, corresponding to the dose of the toxic agent that results in death of 50% of the cells; note that the scale is logarithmic. Each symbol represents a different individual bird with one bird from each of 19 different species. All cell lines were derived using 20% O₂, cryopreserved, and then expanded for two passages at 3% O₂ before testing in 3% O₂. (M) and (R) symbols indicate mean LD₅₀ values detected in a previous set of experiments (Harper et al., 2007) using the same methods. MMS = methyl methanesulfonate. Units for LD₅₀ are μM (cadmium and H₂O₂) and mM (paraquat and MMS).

Figure 2

Legend: Dog fibroblasts are typically more resistant to lethal stress than mouse or rat fibroblasts from wild-caught individuals. There is little to no overlap in the observed values for dog cell lines with mean values of mouse and rat cells. Values shown are LD₅₀’s, corresponding to the dose of the toxic agent that results in death of 50% of the cells; note that the scale is logarithmic only for the cadmium panel. Each symbol represents an individual dog, representing a mixture of purebred and mixed-breed animals (21 – 36 dogs per panel). The dog cell lines were derived using 3% O₂, cryopreserved, and then expanded for two passages at 3% O₂ before testing in 3% O₂. (M) and (R) symbols indicate mean LD₅₀ values detected in a previous set of experiments (Harper et al., 2007) using the same methods, except that the O₂ tension was 20%. Pilot studies using mouse cell lines have indicated no consistent effect of initial O₂ tension on LD₅₀ values, regardless of test condition (not shown). Units for LD₅₀ are μM (cadmium and H₂O₂) and J/m² (UV).