25 years ago we first applied the
theory to explain aging of biological species [1,2]. Since that time we
continued the development of this theory [3-5] and came to the
(1) Redundancy is a key notion for
and the systemic nature of aging in particular. Systems, which are
redundant in numbers of irreplaceable elements, do deteriorate (i.e.,
age) over time, even if they are built of non-aging elements.
apparent aging rate or expression of aging (measured as age differences
in failure rates, including death rates) 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) as well as the observed late-life mortality
deceleration, leveling-off, and mortality plateaus.
organisms seem to be formed with a high load of initial damage, and
therefore their lifespan and aging patterns may be sensitive to
early-life conditions that determine this initial damage load during
The idea of early-life programming of aging and longevity may have important practical implications for developing early-life interventions promoting health and longevity. The theory also suggests that aging research should not be limited to studies of qualitative changes (like age changes in gene expression), because changes in quantity (numbers of cells and other functional elements) could be more important driving force of aging process.
An introductory section presented
earlier is written as an abstract
briefly summarizing the main ideas, findings and conclusions of our
previous studies. The purpose of this section is to provide a more
general discussion of the reliability-engineering approach to the
problem of biological aging. This discussion is focused on very broad
substantive issues, because mathematical formalism and biological
details are already published elsewhere [1-5]
There may be several
different research strategies in attempts to understand the nature of
the aging process. The prevailing research strategy now is to focus on
the molecular level in the hope of understanding the proverbial nuts
and bolts of the aging process. In accordance with this approach, many
aging theories explain aging of organisms through aging of organisms'
components. However, this circular reasoning of assuming aging in
order to "explain" aging leads to a logical contradiction, because
moving in succession from the aging of organisms to the aging of
organs, tissues, and cells, we eventually come to atoms, which are
known not to age.
Thus we come to the following basic
question on the
origin of aging: How
can we explain the aging of a system built of
non-aging elements? This question invites us to start thinking
the possible systemic nature of aging and to wonder whether aging may
be a property of the system as a whole. In other words, perhaps we need
to broaden our vision and be more concerned with the bigger picture of
the aging phenomenon rather than its tiny details. To illustrate the
need for a broad vision, consider the following questions:
-- Would it be possible to understand a newspaper article by looking at it through an electronic microscope?
-- Would the perception of a picture in an art gallery be deeper and more comprehensive at the shortest possible distance from it?
A good example of a broad vision of the
is provided by the evolutionary theories of aging [6-8]. Evolutionary
perspective helps to stay focused on a bigger picture, and to avoid
overwhelming by billions of tiny details. Evolutionary theories
demonstrate that taking a step back from too close consideration of the
details over "the nuts and bolts" of the aging process helps to gain a
broader vision of the aging problem.
The remaining question is whether
the evolutionary perspective represents the ultimate general
theoretical framework for explanations of aging. Or perhaps there may
be even more general theories of aging, one step further removed from
the particular details?
The main limitation of evolutionary
aging is that they are applicable to reproducing organisms only,
because these theories are based on the idea of natural selection and
on the declining force of natural selection with age.
However, aging is
a very general phenomenon -- it is also observed in technical devices
(like cars), which do not reproduce themselves in a sexual or any other
way and which are, therefore, not subject to evolution through natural
Thus, there may exist a more general
explanation of aging,
beyond the evolutionary theories. The quest for a general explanation
of aging (age-related increase in failure rates), applicable both to
technical devices and biological systems invites us to consider the
general theory of systems failure known as reliability theory [1-5].
Interestingly, the reliability theory
suggests that we reevaluate the
old belief that aging is somehow related to limited economic or
evolutionary investments in systems' longevity. The theory provides a
completely opposite perspective on this issue--that aging is a direct
consequence of investments into systems reliability and durability
through enhanced redundancy. This is an important statement, because it
helps to explain why the expression of aging (age-associated
differences in failure rates) might be more profound in more
complicated redundant systems, designed for higher durability .
theory also suggests that research on aging should not be limited to
the studies of qualitative changes (such
as age-related changes in gene expression), because changes in quantity
in (numbers of cells and other functional elements) could be an
important driving force of the aging process. In other words, aging
might be largely driven by a process of redundancy loss [5,9].
Reliability theory predicts that a
system may deteriorate with age even
if it is built from nonaging elements with constant failure rates
The key issue here is the system's redundancy for irreplaceable
elements, which is responsible for the aging phenomenon. In other
words, each particular step of system destruction or deterioration may
seem to be random (no aging, just occasional failure by chance), but if
a system failure requires a sequence of several such steps (not just a
single step of destruction), then the system as a whole may have an
aging behavior. Why is this conclusion important? Because the
significance of beneficial health-promoting interventions is often
undermined by claims that these interventions are not proven to delay
the process of aging itself, but instead that they simply delay or
cover up some particular manifestations of aging.
In contrast to these
pessimistic views, reliability theory says that there might be no
specific underlying elementary aging process; instead, aging might be
largely a property of a redundant system as a whole, because it has a
network of destruction pathways, each being associated with particular
manifestations of aging (types of failure). Therefore, we should not be
discouraged by only partial success of each particular intervention,
but instead we can appreciate that we might have many opportunities to
oppose aging in numerous different ways.
Thus, the efforts to
understand the routes and early stages of age-related degenerative
diseases should not be discarded as irrelevant to understanding true
biological aging. On the contrary, attempts to build an intellectual
firewall between biogerontological research and clinical medicine are
counterproductive. After all, the main reason why people are really
concerned about aging is because it is related to health deterioration
and increased morbidity. The most important age-related changes, with
respect to quality of life, are those that make older people sick and
Reliability theory suggests general
answers to both the "why"
and the "how" questions about aging. It explains why aging occurs by
identifying the key determinant of aging behavior: system redundancy in
numbers of irreplaceable elements. Reliability theory also explains how
aging occurs, by focusing on the process of redundancy loss over time
as the major mechanism of aging. It is perfectly compatible with
evolutionary theories of aging, and it helps to identify key
components, which might be important for the evolution of species
reliability and durability (longevity): initial redundancy levels, rate
of redundancy loss, and repair potential. Moreover, 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.
Aging is a complex phenomenon, and a holistic approach using reliability theory may help to analyze, understand, and perhaps control it. We suggest, therefore, that reliability theory should be added to the arsenal of methodological approaches applied in research on aging.
This study was made possible thanks to a generous support from the National Institute on Aging (NIH, USA), and a stimulating working environment at the Center on Aging, NORC/University of Chicago. We would like to thank members of the Science Advisory Board, SAB (http://www.scienceboard.net/) for useful comments on our work made at the SAB discussion group.