Revival: Biological Effects of Low Level Exposures to Chemical and Radiation (1992)

HYPOTHESES ON LONGEVITY HORMESIS 13

ity hormesis appears to be such a response; its reversibility serves to keep it

economical.

Hypothesis X: When, through exposure to nonessential, exogenous agents

or stimuli, longevity hormesis is elicited in homogeneous laboratory popula­

tions of eutherian mammals housed under uniform, good laboratory condi­

tions and kept free of preventable disease, toxicity, if also induced, is most

likely to be of the irreversible kind.

In searching the literature for mortality data in laboratory populations,

the most frequently located data come from studies in which exogenous

agents are administered at a constant rate. When toxicity is observed, with

or without concomitant longevity hormesis, it most frequently is the irre­

versible kind; longevity hormesis, by definition, is reversible. Assuming

both irreversible toxicity and reversible hormesis are deposited onto the

linear Gompertz function at a zero-order rate, and further assuming longev­

ity hormesis dissipates at a first-order rate, one obtains the following Gom­

pertz function:1824’25

where 7 X represents the irreversible accumulation of toxicity injury and the
far right term reflects the reversible longevity hormetic effect.
Obviously both 7 and X will be dependent on the dose of exogenous
agent. Neafsey et al.24 25 empirically found that the logarithmic-logistic
function,64-74 also known as the sigmoid Emax model, generalized hyperbolic
function, and Hill equation, characterized the dose-response relationships
remarkably well. This is not to imply that toxicity and longevity hormesis
processes obey the underlying assumptions inherent in this equation, but
rather that the large number of parameters in the logarithmic-logistic equa­
tion provide superior flexibility in curve-fitting equations to data. It is
therefore not surprising that in the examples cited below, Equation 12 (or a
“collapsed” version) is most frequently employed.
In generalized nomenclature, the logarithmic-logistic equation may be
expressed as follows:

(13)

( 14 )

where R = response

Rm = maximum response

D = dose