Thursday, September 17, 2015

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-- Leonid  and  Natalia

-- Leonid Gavrilov, Ph.D., GSA Fellow
-- Natalia Gavrilova, Ph.D., GSA Fellow
Center on Aging, NORC at the University of Chicago


Reliability theory of aging and longevity is a scientific approach aimed to gain theoretical insights into mechanisms of biological aging and species survival patterns by applying a general theory of systems failure, known as reliability theory.



Reliability theory allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Applications of reliability-theory approach to the problem of biological aging and species longevity lead to the following conclusions:
  1. Redundancy is a key for understanding aging and the systemic nature of aging in particular. Systems, which are redundant in numbers of irreplaceable elements, do deteriorate (that is, age) over time, even if they are built of non-aging elements.
  2. Paradoxically, the apparent aging rate or expression of aging (measured as relative differences in failure rates between compared age groups) is higher for systems with higher redundancy levels.
  3. Redundancy exhaustion over the life course explains the observed 'compensation law of mortality' (mortality convergence at later life, when death rates are becoming relatively similar at advanced ages for different populations of the same biological species), as well as the observed late-life mortality deceleration, leveling-off, and mortality plateaus.
  4. Living organisms seem to be formed with a high initial load of damage (HIDL hypothesis), and therefore their lifespan and aging patterns may be sensitive to early-life conditions that determine this initial damage load during early development. The idea of early-life programming of aging and longevity may have important practical implications for developing early-life interventions promoting health and longevity.
  5. Reliability theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms "prefer" to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Theoretical conditions are specified when organisms die according to the Weibull law: organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law.
  6. Reliability theory helps evolutionary theories to explain how the age of onset of deleterious mutations could be postponed during evolution, which could be easily achieved by a simple increase in initial redundancy levels. From the reliability perspective, the increase in initial redundancy levels is the simplest way to improve survival at particularly early reproductive ages (with gains fading at older ages). This matches exactly with the higher fitness priority of early reproductive ages emphasized by evolutionary theories. Evolutionary and reliability ideas also help in understanding why organisms seem to "choose" a simple but short-term solution of the survival problem through enhancing the systems' redundancy, instead of a more permanent but complicated solution based on rigorous repair (with the potential of achieving negligible senescence). Thus there are promising opportunities for merging the reliability and evolutionary theories of aging.
Overall, the reliability theory provides a parsimonious explanation for many important aging-related phenomena and suggests a number of interesting testable predictions. Therefore, reliability theory seems to be a promising approach for developing a comprehensive theory of aging and longevity integrating mathematical methods with specific biological knowledge and evolutionary ideas.
Reliability theory of aging provides an optimistic perspective on the opportunities for healthy life-extension. According to reliability theory, human lifespan is not fixed, and it could be further increased through better body maintenance, repair, and replacement of the failed body parts in the future.

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