Reliability theory of aging and longevity

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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.

Overview[edit]

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.

See also[edit]

References[edit]

  • Gavrilov LA, Gavrilova NS. Reliability Theory of Aging and Longevity. In: Masoro E.J. & Austad S.N.. (eds.): Handbook of the Biology of Aging, Sixth Edition. Academic Press. San Diego, CA, USA, 2006, 3-42. ISBN 0-12-088387-2
  • Gavrilov LA, Gavrilova NS. Models of Systems Failure in Aging. In: P Michael Conn (Editor): Handbook of Models for Human Aging, Burlington, MA : Elsevier Academic Press, 2006. 45-68. ISBN 0-12-369391-8.
  • Gavrilov LA, Gavrilova NS. Why We Fall Apart. Engineering's Reliability Theory Explains Human Aging. IEEE Spectrum, 2004, 41(9): 30-35.
  • Gavrilov LA, Gavrilova NS. The Reliability-Engineering Approach to the Problem of Biological Aging. Annals of the New York Academy of Sciences, 2004, 1019: 509-512. PMID 15247076
  • Gavrilov L.A., Gavrilova N.S. The quest for a general theory of aging and longevity. Science's SAGE KE (Science of Aging Knowledge Environment) for 16 July 2003; Vol. 2003, No. 28, 1-10. http://sageke.sciencemag.org, PMID 12867663
  • Gavrilov L.A., Gavrilova N.S. The reliability theory of aging and longevity. Journal of Theoretical Biology, 2001, 213(4): 527-545. doi:10.1006/jtbi.2001.2430 PMID 11742523
  • Abernethy, John. Gompertzian mortality originates in the winding-down of the mitotic clock. Journal of Theoretical Biology, 1998, 192, 419-435.
  • Leonid A. Gavrilov & Natalia S. Gavrilova (1991), The Biology of Life Span: A Quantitative Approach. New York: Harwood Academic Publisher, ISBN 3-7186-4983-7
  • Gavrilov, L.A. A mathematical model of the aging of animals. Proc. Acad. Sci. USSR [Doklady Akademii Nauk SSSR], 1978, 238(2): 490-492. English translation by Plenum Publ Corp: pp.53-55. PMID 624242
  • Abernethy JD. The exponential increase in mortality rate with age attributed to wearing-out of biological components. Journal of Theoretical Biology, 1979, 80, 333-354.
  • Gavrilov, L.A., Gavrilova, N.S., Yaguzhinsky, L.S. The main regularities of animal aging and death viewed in terms of reliability theory. J. General Biology [Zhurnal Obschey Biologii], 1978, 39(5): 734-742. PMID 716614
  • Witten, T.M., Investigating the aging mammalian system: Cellular levels and beyond, Proc. 25th Annual Meeting of the Society for General Systems Research, (1981) 309-315.
  • Witten, T.M., A return to time, cells, systems, and aging: I. Rethinking the concepts of senescence in mammalian systems, Mech. Aging and Dev., 21(1983)69-81.
  • Witten, T.M., A return to time, cells, systems, and aging: II. Relational and reliability theoretic aspects of senescence in mammalian systems, Mech. Aging and Dev., 27 (1984) 323-340.
  • Witten, T.M., Reliability theoretic methods and aging: Critical elements, hierarchies, and longevity---Interpreting survival curves, (in) The Molecular Biology of Aging (eds.) A. Woodhead, A. Blackett, and R. Setlow (Plenum Press, N.Y. 1985).
  • Witten, T.M., A return to time, cells, systems and aging: III. Critical elements, hierarchies, and Gompertzian dynamics, Mech. Ageing and Dev., 32 (1985) 141-177.
  • Witten, T.M., A return to time, cells, system, and aging: IV. Further thoughts on Gompertzian survival dynamics---The neonatal years, Mech. Aging and Dev., 33 (1985) 177-190.
  • Witten, T.M., Information content of biological survival curves arising in aging experiments: Some further thoughts, (in) Evolution of Aging Processes in Animals (ed.) A. Woodhead and K.H. Thompson (Plenum Press, N.Y., 1987).
  • Witten, T.M., A return to time, cells, systems, and aging: V. Further thoughts on Gompertzian survival dynamics --- the geriatric years, Mech. Aging and Dev., 46(1988) 175-200.

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