Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

Abstract

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest age.

Testing the heterogeneity theory of late-life mortality plateaus by using cohorts of Drosophila melanogaster

“…Brooks et al (1994) demonstrated that mortality rate in an isogenic population of the nematode Caenorhabditis elegans showed a less-distinct plateau than in a genetically heterogeneous population, but Vaupel et al (1994) were quick to point out that the isogenic line was grown at a higher temperature and in higher food concentration than the heterogeneous line, greatly complicating the interpretation of the mortality patterns. In addition, isogenic versus heterogenous populations of Drosophila melanogaster do not consistently show these same patterns (Curtsinger et al, 1992;Fukui et al, 1996). Furthermore, although the relevance of individual environmental heterogeneity to late-life mortality rates is extremely difficult to test effectively (Curtsinger et al, 1992;Fukui et al, 1993;Vaupel and Carey, 1993), an intricate experiment by Khazaeli et al (1998) found no evidence to support the hypothesis that environmental heterogeneity among individual flies is a primary factor in determining late-life mortality rates.…”

“…In addition, isogenic versus heterogenous populations of Drosophila melanogaster do not consistently show these same patterns (Curtsinger et al, 1992;Fukui et al, 1996). Furthermore, although the relevance of individual environmental heterogeneity to late-life mortality rates is extremely difficult to test effectively (Curtsinger et al, 1992;Fukui et al, 1993;Vaupel and Carey, 1993), an intricate experiment by Khazaeli et al (1998) found no evidence to support the hypothesis that environmental heterogeneity among individual flies is a primary factor in determining late-life mortality rates. In another experiment, Khazaeli et al (1995b) seemingly demonstrated environmental heterogeneity for stress resistance by subjecting genetically homogenous populations to a 24-hr heat stress and comparing their poststress mortality patterns to control lines; however, this paper was later retracted after new research revealed that the experimental method was flawed Khazaeli et al, 1997;Tatar et al, 1997).…”

“…Because late-life plateaus in cohort mortality rates indicate that there is no "wall of death" past which no organism can survive, some individuals can theoretically live indefinitely. Understandably, researchers have been intrigued by this phenomenon since its first experimental demonstration (Carey et al, 1992;Curtsinger et al, 1992). Indeed, late-life mortality plateaus seem to challenge current definitions and theories of aging (see Finch, 1990;Rose, 1991).…”

“…The required heterogeneity may be genetic or environmental (cf. Curtsinger et al, 1992;Fukui et al, 1993).…”

Rules for the use of model organisms in antiaging pharmacology

“…In some other organisms, such as Pacific salmon and the marsupial Antechinus , there is a spectacular period of aging which proceeds so rapidly that no individuals survive after the aging phase. But in many animals, we now know, there is a period after aging during which mortality and fecundity plateau (Carey et al ., 1992;Curtsinger et al ., 1992;Vaupel et al ., 1998;Rauser et al ., 2003). That is, aging stops, and a new phase of life begins Rauser et al ., 2006).…”