Aging:
Reliability Theory and
Phenoptosis Concept
Leonid A. Gavrilov
Natalia S. Gavrilova
Center on Aging, NORC/University of Chicago,
1155 East 60th Street, Chicago, IL 60637
Suppose, for the sake of
discussion, that the ‘Program’
exists.
Then what properties should
this ‘Program’ have?
FACT:
Genetically identical
organisms living in identical
conditions do NOT die
simultaneously
In fact the range (variance) in
lifetimes remains quite high.
Coefficient of variation =
variance
 30%
mean
Implications:
The hypothetical ‘Program’ is
NOT a program for lifespan
(length of life), but rather a
program for age-dynamics for
probability of death
FACT:
Age-related increase in death
risk (aging) starts very early.
Aging is observed long before
post-reproductive age,
sometimes as early as at
puberty
Stages of Life in Machines and Humans
The so-called bathtub curve for
technical systems
Bathtub curve for human mortality as
seen in the U.S. population in 1999
has the same shape as the curve for
failure rates of many machines.
Implications:
The hypothetical ‘Program’ is not a
post-reproductive program based on a
principle:
“Мавр сделал свое дело, мавр
должен уходить”
Instead it should be a maturationrelated program based on a principle:
“Мавр начал свое дело, мавр может
начинать потихоньку уходить”
How can this hypothetical
‘Program’ be sustained by
Nature (evolution)?
If such Program exists then
how its accidental switchingoff (by random mutations) can
be harmful for fitness (number
of progeny)?
General Idea:
Military equipment designed for
combat may have ‘suicidal’ mode of
operation (e.g. missiles), sometimes
even with programmed selfdestruction.
This may happen in biology too, if “the
struggle for survival” and “biological
arms race” are operating literally.
Idea:
Programmed death as a way to save
progeny from more dangerous, hostadapted “familial” infections.
Justification:
Over time, infections can evolve within an
organism (microevolution), producing vectors
well-adapted to a particular host, and his closest
relatives.
Making parental lifespan shorter saves the
progeny from the emergence of such
particularly dangerous family-specific infections
Excessive apoptosis and killing
of our infected cells by immune
system may be advantageous
for our progeny (lower risk of
family-specific infections), but
it results in aging due to cell
loss.
Idea:
Creating a toxic, self-destructive
environment within our own
body, in order to control
infections.



Chronic inflammation including the
chemical weapons (ROS, HClO, etc.)
Intentional deficits of micronutrients
(iron deficiency, etc.) to control
infectious growth at the cost of
organism’s damage (mutations)
High body temperature, even at
baseline, even if not good for longevity
(depurinization of DNA)
Other Ideas:
“Developmental rush –>
Developmental noise” hypothesis
Selective pressure to complete
development sooner rather than later
creates opportunities for more ‘mistakes’
introduced during development – “the
high initial damage load hypothesis” (HIDL
hypothesis).
Consensus between stochastic
and programmed aging:


Aging is stochastic, because this is a
progressive accumulation of random
damage
Aging may also be considered as
programmed, because of specific
mechanisms responsible for elevated
rates of damage accumulation
Implications for life extension
If these ideas are correct,
then our bodies are not
optimized for a long life, and
there are a lot of
opportunities for further
very significant extension of
healthy lifespan