Heterogeneous stocks and selective breeding in aging research

There are advantages and limitations to using genetically heterogeneous stocks and selective breeding procedures in gerontological and healthspan research. Animal models that address complex systems of aging involve constraint or manipulation of genetic diversity. They derive from levels of genetic analysis ranging from molecular to quantitative and are relevant to levels of causal hierarchy from base sequences to complex multivariate phenotypes. For some research purposes control of the genotypic source of phenotypic variability by fi xation is desirable; others involve establishing genetic diversity or deliberately manipulating identifi ed genes or anonymous gene complexes to specifi cation. Genetic heterogeneity is essential or advantageous for multivariate description of complex phenomena, the examination of associations among variables, or manipulation of polygenic systems. This review concentrates on these latter quantitative requirements. Space limitations preclude a comprehensive review, but relevant sample references and some hints of historical perspectives are provided, with apologies to the many relevant authors not cited.