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

HYPOTHESES ON LONGEVITY HORMESIS 5

THE HYPOTHESES

The Moving Finger writes; and, having writ,

Moves on: nor all thy Piety nor Wit

Shall lure it back to cancel half a Line,

Nor all thy Tears wash out a Word of it.

Rubaiyat of Omar Khayyam29

Hypothesis I: Mammalian senescence is “progressive instability that arises
from a slow and continuing change of constraints as a by-product of energy
throughput and action.”

This hypothesis, proposed by Yates,830 evinces the view that “entropy

accumulation shrinks the viability reserves of the organism and renders it

more susceptible to the action of fluctuations.” The view that “constraints

shall not last,” a reiteration of the second law of thermodynamics, sub­

sumes the idea of mammalian senescence and assures that progressive dete­

rioration of bodily faculties and performances will occur “(the moving fin­

ger)” as we grow old.81630 Deterioration occurs because the rate of

endogenous damage exceeds the rate of endogenous repair. From the point

of view of Asimov, aging is inevitable, because the “significant chemicals of

living tissue are rickety and unstable, which is exactly what is needed for

life.”31

Many investigators (see especially Cutler32) believe senescence occurs pri­

marily as a result of oxygen metabolism; these reactions produce free radi­

cals, aldehydes, and a wide range of peroxides highly toxic to cells. Cutler32

speculates that the by-products of oxidations damage vital cellular compo­

nents, causing cells to drift from their proper state of differentiation to a

state of dysdifferentiation. One interesting example of cellular dysdifferen-

tiation is the synthesis of hemoglobin by neuron cells.32 Bass et al.33 devel­

oped a mortality model along the same lines. They derived a Gompertz-

Makeham function by assuming a competition between hypothetical

life-prolonging and life-shortening regulatory elements (ultimately won by

the latter) interacting by generalized Volterra-type competitive exclusion.

On a systems level, it appears that aging is regulated principally through

integrative mechanisms involving mainly the brain, the endocrine glands,

and the immune tissues.34 Collectively, these elements constitute what has

come to be known as the neuroendocrinimmune system.

Hypothesis II: Mammalian toxicity is an instability arising from a decay of

constraints, instigated by exposure to nonessential, noxious exogenous

agents/stimuli or overexposure to essential agents/stimuli.

Armed with Hypotheses I and II, we attempt to differentiate senescence

from toxicity. The former arises as the “cost of living” from essential pro­

cesses; the latter is a consequence of deleterious processes provoked by

unnecessary, exogenous insults or exposures. Of course, it is not always easy