Aging: Reliability Theory and Phenoptosis Concept

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AgingReliability Theory and Phenoptosis Concept

• Leonid A. Gavrilov
• Natalia S. Gavrilova
• Center on Aging, NORC/University of Chicago,
• 1155 East 60th Street, Chicago, IL 60637

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Suppose, for the sake of discussion, that the
Program exists.Then what properties should
this Program have?
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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
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ImplicationsThe hypothetical Program is NOT
a program for lifespan (length of life), but
rather a program for age-dynamics for probability
of death
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FACTAge-related increase in death risk (aging)
starts very early.Aging is observed long before
post-reproductive age, sometimes as early as at
puberty
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Stages of Life in Machines and Humans
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.
The so-called bathtub curve for technical systems
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ImplicationsThe hypothetical Program is not
a post-reproductive program based on a
principle???? ?????? ???? ????, ???? ??????
???????Instead it should be a
maturation-related program based on a
principle???? ????? ???? ????, ???? ?????
???????? ?????????? ???????
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How can this hypothetical Program be
sustained by Nature (evolution)?If such Program
exists then how its accidental switching-off (by
random mutations) can be harmful for fitness
(number of progeny)?
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General IdeaMilitary equipment designed for
combat may have suicidal mode of operation
(e.g. missiles), sometimes even with programmed
self-destruction.This may happen in biology
too, if the struggle for survival and
biological arms race are operating literally.
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Idea

• Programmed death as a way to save progeny from
  more dangerous, host-adapted 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

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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.
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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 organisms damage (mutations)
• High body temperature, even at baseline, even if
  not good for longevity (depurinization of DNA)

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Other Ideas

• Developmental rush gt 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).

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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

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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