HYPOTHESES ON LONGEVITY HORMESIS 3The time at which Qx is operative is taken as the midtime of the interval. A
variance estimate for [In ftx] may also be readily calculated.214 The recipro
cal of this variance estimate is appropriate for weighting the dependent
variable in linear or nonlinear least squares analysis (see below).
As a means of investigating the usefulness of Gompertz analysis in the
characterization of mammalian aging, toxicity, and longevity hormesis, a
series of hypotheses will initially be posited and discussed. This will be
followed by a more in-depth discussion of longevity hormesis, including a
survey and evaluation of the database. As used here, the term hypothesis is
applied in a general sense, referring to a proposition or declaration that has
not yet attained a high degree of credibility,15 a conception of what the truth
might be.16 Consequently, a hypothesis is capable of being believed,
doubted, or denied.17 Moreover, some of the hypotheses presented may
appropriately be perceived as empirical observations, statements of fact,
postulates, paradigms, models, theories, etc. However, these distinctions
will not be attempted by the author.
Of paramount interest is the concept of longevity hormesis, characteriza
tion of which is facilitated through Gompertz analysis. Unfortunately, even
the generic concept of hormesis has trod a tortuous path,18 with many not
believing in its existence. Nonetheless, a historically based definition of
hormesis will be posited for heuristic purposes: hormesis is a biological
phenomenon in which a beneficial or stimulatory effect is obtained through
application of a biologically nonessential agent generally considered detri
mental or toxic to the system under scrutiny.
Obviously, this definition is unsettling. For one thing, a stimulatory
response may not be beneficial, e.g., induction of microsomal enzymes that
increase production of mutagens and carcinogens. Another difficulty arises
in reconciling the diverse processes that have been declared hormetic:
growth, development, hatching success, length of reproductive life, behav
ioral parameters, microsomal enzyme induction, fecundity, cancer reduc
tion, disease resistance, viability, respiration, radiation resistance, wound
healing, resistance to infection, DNA repair, immune system stimulation,
and longevity enhancement.18 In essence, the concept of hormesis rests upon
biological process descriptions, the linchpins of which are subjective judg
ments as to whether or not the processes are “good” for the organism and/
or species.19 Making matters worse, mechanisms underlying these so-called
hormetic responses are either poorly understood or not understood at
all. 18 20-22 Despite these problems, there do exist some phenomena, labeled
hormetic, that are intriguing because they are counter-intuitive. A good
example is growth hormesis in peppermint.23 Application of low concentra
tions of the growth retardant phosfon actually stimulates growth of the
plant.
Another example is longevity hormesis.5’18’21’24’25 Longevity hormesis is a
phenomenon of unknown mechanism whereby an exogenous agent revers
ibly acts to reduce age-specific mortality rates (relative to controls), in