Page 217 - 20dynamics of cancer

10 Aging

This chapter analyzes age-specific incidence for the leading causes of
death. I discuss the incidence curves for mortality in light of multistage
theories for cancer progression. This broad context leads to a general
multicomponent reliability model of age-specific disease.
The first section describes the age-specific patterns of mortality for
the twelve leading causes of death in the USA. Heart disease and vari-
ous other noncancer causes of death share two attributes. From early
life until about age 80, the acceleration in mortality increases in an ap-
proximately linear way. After age 80, mortality decelerates sharply and
linearly for the remainder of life. By contrast, cancer and a couple of
other causes of death follow a steep, nearly linear rise in mortality up to
40–50 years, and a steep, nearly linear decline in acceleration later in life.
The late-life deceleration of aggregate mortality over all causes of death
has been discussed extensively during the past few years (Charlesworth
and Partridge 1997; Horiuchi and Wilmoth 1998; Pletcher and Curtsinger
1998; Vaupel et al. 1998; Rose and Mueller 2000; Carey 2003).
The second section presents two multistage hypotheses that fit the
observed age-specific patterns of mortality. The increase in acceleration
through the first part of life may be explained by a slow increase in the
transition rate between stages—perhaps a slow increase in the failure
rate for components that protect against disease. With regard to the late-
life decline in acceleration, all multistage models produce a force that
pushes acceleration down at later ages. That downward force comes
from the progression of individuals, as they grow older, through the
early stages of disease.
The third section expands the multistage theory of cancer to a broader
reliability theory of mortality. For cancer, genetic and morphological ob-
servations support the idea that tumor development progresses through
a sequence of stages. For other causes of death, little evidence ex-
ists with regard to stages of progression. A multicomponent reliability
framework seems more reasonable: the reliability (lifespan) of organ-
isms may depend on the rates of failure of various component subsys-
tems that together determine disease progression and survival. Multi-
stage progression corresponds to multiple components arranged in a