The Quest for the General Theory of Aging and Longevity

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The Quest for the General Theory of Aging
and Longevity

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

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Aging is a Very General Phenomenon!
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• Naive but important question on the origin of
  aging
• How to explain aging of the system built of
  non-aging elements?
• This question is important for understanding the
  systemic component of aging (aging of the system
  as a whole) because
• Many aging theories are "explaining" aging of the
  system through aging of its components. However,
  this circular reasoning of assuming aging in
  order to "explain" aging leads us to a logical
  blind alley, because moving in succession from
  the aging of the organism to the aging of organs,
  tissues and cells, we eventually come to atoms,
  which are known not to age.
• Thus, the key to the explanation of aging is the
  question How do we explain the aging of a system
  constructed out of non-aging components?

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What Should the Aging Theory Explain

• Why do most biological species deteriorate with
  age?
• Specifically, why do mortality rates increase
  exponentially with age in many adult species
  (Gompertz law)?
• Why does the age-related increase in mortality
  rates vanish at older ages (mortality
  deceleration)?
• How do we explain the so-called compensation law
  of mortality (Gavrilov Gavrilova, 1991)?

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Compensation Law of MortalityConvergence of
Mortality Rates with Age

• 1 India, 1941-1950, males
• 2 Turkey, 1950-1951, males
• 3 Kenya, 1969, males
• 4 - Northern Ireland, 1950-1952, males
• 5 - England and Wales, 1930-1932, females
• 6 - Austria, 1959-1961, females
• 7 - Norway, 1956-1960, females
• Source Gavrilov, Gavrilova,
• The Biology of Life Span 1991

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Mortality at Advanced Ages

• Source Gavrilov L.A., Gavrilova N.S. The
  Biology of Life Span
• A Quantitative Approach, NY Harwood Academic
  Publisher, 1991

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M. Greenwood, J. O. Irwin. BIOSTATISTICS OF
SENILITY
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Redundancy Creates Both Damage Tolerance and
Damage Accumulation (Aging)
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Why Organisms May Be Different From Machines?
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Differences in reliability structure between (a)
technical devices and (b) biological systems
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Mortality Kinetics in Highly Redundant Systems
Saturated with Defects
Failure rate of a system is described by the
formula
where n is a number of mutually substitutable
elements (connected in parallel) organized in m
blocks connected in series k - constant
failure rate of the elements i - is a number
of initially functional elements in a block ?
- is a Poisson constant (mean number of initially
functional elements in a block). Source
Gavrilov L.A., Gavrilova N.S. The reliability
theory of aging and longevity. Journal of
Theoretical Biology, 2001, 213(4) 527-545.
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Dependence of the logarithm of mortality force
(failure rate) on age for binomial law of
mortality
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Conclusions (I)

• REDUNDANCY is a key for understanding aging and
  the systemic nature of aging in particular
  Systems, which are redundant in numbers of
  irreplaceable elements will always deteriorate
  (age) over time, even if they are built of
  non-aging elements.
• Apparent aging rate or expression of aging  (age
  differences in failure rates, including death
  rates) is increasing with higher redundancy
  levels.
• REDUNDANCY EXHAUSTION over the life course is
  responsible for the "compensation law of
  mortality" (mortality convergence at later life)
  as well as for the "late-life mortality
  deceleration, levelling-off and mortality
  plateaus"
• Organisms seems to be formed with high LOAD OF
  INITIAL DAMAGE and, therefore, their lifespan and
  aging patterns may be sensitive to EARLY-LIFE
  CONDITIONS, which determine this initial damage
  load during early development. Implications
  potentially great opportunities for anti-aging
  interventions if started extremely early (before
  birth?).

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Conclusions (II)

• Aging studies should not be limited to the
  studies of qualitative changes (like age changes
  in gene expression), because changes in QUANTITY
  (numbers of cells and other functional elements)
  could be the driving force of aging process.
  Aging may be driven by a process of redundancy
  loss.
• Lifespan is not fixed  -- there is no absolute
  specific limit to the duration of life. Limits
  are in our minds only.
• SUGGESTION It is important to demystify aging
  and to begin considering it as not a mysterious
  and immutable process, but rather as a
  collection of destruction pathways, many of which
  are already known as pathways for specific
  age-related degenerative diseases. Therefore,
  separation of aging and diseases is worthless and
  counter-productive.

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Acknowledgments

• This study was made possible thanks to
• generous support from the National Institute on
  Aging, and
• stimulating working environment at the Center
  on Aging, NORC/University of Chicago