4 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
addition to any other actions elicited by the agent. This is not intended to be
a definition of longevity hormesis, but rather a vague description of it. A
proper definition awaits delineation of mechanism (see Neafsey21 for a
review of proposed mechanisms). For longevity hormesis to be operative, it
is not required that observed (net) age-specific mortality rates be reduced
relative to control animals, since toxicity from the agent may predominate
and actually bring about an overall increase in age-specific mortality. All
that is required is that some hormetic biological activity exists that reduces
age-specific mortality rates from values that theoretically would be present
in the absence of this activity. In the simplest case, an agent only produces
longevity hormesis; that is, toxicity and other effects are completely absent.
In this situation, only reductions in age-specific mortality rates would theo
retically occur. When this occurs in practice, it is generally accompanied by
decreases in age-associated pathologies.24 26
Unfortunately, this situation occurs infrequently with data from the liter
ature. More often, both longevity hormetic and toxic actions elicited by an
agent are simultaneously observed, mainly because most data come from
studies in which toxic effects are being investigated, for example, risk
assessment (bioassay) rodent studies. With the exception of antioxidant
feeding studies, caloric restriction studies, and physical activity studies, it is
difficult to find experiments specifically designed to demonstrate life pro
longation in animal populations, especially mammals. And even when these
studies are found, one frequently cannot make plots of age-specific mortal
ity rates vs time. Investigators frequently report only mean or median life
spans, especially when studying insect populations such as Drosophila (fruit
flies).
Another confounding variable encountered in literature data is life pro
longation caused by reduced caloric intake and/or suppressed weight gain.
Administration of exogenous agents, especially toxic ones, and especially
those admixed with food, often causes rodents to eat less and gain less
weight. This reduced food consumption/suppressed weight gain is associ
ated with an irreversible (permanent) longevity enhancement, unrelated to
longevity hormesis.21 24 25 27 28 The two types of longevity enhancement, that
from caloric restriction (irreversible) vs that from longevity hormesis
(reversible), must not be confused.
As mentioned earlier, many of the concepts advanced in this chapter will
be discussed in the context of hypotheses. Since longevity hormesis is
described in terms of the Gompertz function, and since the Gompertz func
tion is dependent upon aging and toxicity, as well as longevity hormesis, it is
not possible to omit hypotheses dealing with these biological phenomena. A
thorough knowledge of how all these processes affect the Gompertz func
tion is necessary for an understanding of longevity hormesis. Accordingly,
the database characterizing the longevity hormesis phenomenon will only be
discussed after a proper foundation has been laid.