The approach of Blangero (1993), which is framed in terms of the statistical genetic theory of genotype × environment (G × E) interaction, is used to address human senescence. Because of the interest in senescence, this dissertation focuses on a specific class of G × E interaction, namely genotype × age interaction, where the age continuum has commonly been conceptualized as a special class of continuous environments (Hegele, 1992; Zerba and Sing, 1992; Zerba et al., 1996, 2000; Jaquish et al., 1997; Duggirala et al., 2000). For analytic tractability, the growth hormone/insulin-like growth factor I (GH/IGF-I) axis is used as a microcosm of the complex physiology of senescence. Thus, this dissertation is specifically on genotype × age interaction in the GH/IGF-I axis in relation to the biology of senescence. It is common to focus on the components of the GH/IGF-I axis involving just IGF-I and its binding proteins because it is difficult to get a useful measure of GH without requiring overnight stays on the part of study individuals (Neely and Rosenfeld, 1994). For this reason, the GH/IGF-I axis is hereon referred to as the IGF-I axis. This dissertation is also a small part of a comprehensive research project on the statistical genetics of cardiovascular disease (CVD), namely the San Antonio Family Heart Study (SAFHS). CVD is considered to be one of the major diseases of the metabolic syndrome (Reaven, 1988, 1993, 1995, 1999). Given that the overall metabolic dysfunction encompassed by the metabolic syndrome is known to be strongly age-related (Liese et al., 1998), it is perhaps safely assumed that the metabolic syndrome is one of the more complex manifestations of senescence. In other words, the metabolic syndrome is studied here from the perspective of the biology of senescence.
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