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

8 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES

where X is a hybridized parameter proportional to the zero-order rate con­
stant specifying toxicity injury.

Hypothesis VI: Longevity hormesis is a response to a biologically nonessen­
tial, exogenous agent or stimulus that reversibly reduces Gompertzians rela­
tive to a control population without affecting senescence (i.e., G0 or (j>).

This hypothesis, while positing the concept of longevity hormesis, does

little more than empirically describe it. As mentioned previously, a defini­

tion must await characterization of mechanism. Three points are worth

reiterating. First, longevity hormesis is reversible. Second, longevity horme­

sis is presumed to be mediated through a mechanism that does not impact

on senescence, but rather superimposes its effects onto it. And third, lon­

gevity hormesis is only produced by nonessential stimuli. Application of

life-enhancing essential agents (nutrients, vitamins, etc.) promote longevity

through what has been termed a “proper” action.5 Unfortunately, the dis­

tinction between “proper” and “longevity hormetic” enhancement of lon­

gevity is empiric, based solely on our knowledge of process and system.47

While it is possible that biologically essential agents might also prompt a

longevity hormetic response, there is no currently available data demon­

strating this.

In terms of superimposition onto the Gompertz function, longevity hor­

mesis is expressed by a term that reversibly reduces Gompertzians. By way

of example, assume a linear Gompertz function characterizing senescent

aging in concert with a longevity hormetic stimulus that reduces injury at a

zero-order rate; the injury reducing effect, however, is reversible and dissi­

pates at a first-order rate. The function is identical with Equation 10, except

the far right term has a negative sign designating injury reduction:

( 11 )

Although this example denotes one kinetic scheme for input and dissipation
of longevity hormesis, it is emphasized that any appropriate empiric func­
tion may be used. For example, Thompson et al.47 developed a model of
longevity hormesis in wild chipmunks following a single dose of ionizing
radiation; they found that aging apparently promoted the loss of longevity
hormesis. This is in contrast to Equation 11, in which dissipation of longev­
ity hormesis is age-independent.
For a phenomenon to be considered longevity hormetic, reduction in
Gompertzians must be characterized by a Gompertz term different from
that observed with caloric restriction —the implication being that the mech­
anisms are also different. When a linear Gompertz function describes con­
trol animals, caloric restriction usually acts to reduce mortality simply by
reducing c*;28 that is, it slows the rate of endogenous injury generation.