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Living and Dying For Sex
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A Theory of Aging Based on the Modulation of Cell Cycle Signaling by Reproductive Hormones
Richard L. Bowen and Craig S. Atwood*
HPG Axis is Analogous to the LeafApical Meristem Axis
 Development = differentiation
 Senescence = dysregulated growth and development.
The Cost of Reproduction
For similar sized organisms, longevity is inversely correlated
with reproduction and growth rate (Williams, 1966).
Lifespan (yrs.)
Seeds (per yr)
Growth (per yr)
Yellow Poplar
200
30,000
2 feet
Bristle Cone Pine
5000
few
.01 inches
Response
Light (food)
Deprived
Water
Temperature
Leaf Growth



Flower/Fruit
Production



Tree Growth



Email:
Conversely, in an environment of limited light, water and/or
nutrient resources, phytochrome is downregulated.
Examples of Hostile Reproductive Environments
Decreasing Growth Rate and Increasing Longevity
Nutrient Restriction
Yellow Poplar
(Magnoliaceae
Liriodendron
tulipifera)
require increased energy expenditure which the animal
perceives as a hostile reproductive environment.
 This chronic hostile environment (caloric restriction)
decreases fertility by suppressing reproductive-cell cycle
signaling factors. This preserves fertility and slows aging –
awaiting a more friendly environment.
Phone:
 Growth = cell division and endoreduplication
Phone:
 Change = growth, development and senescence
Cold - sub-arctic
Bristle Cone
Pine
(Pinus
longaeva)
Climbing Plants
Thorny Trees
 Climbing plants and
thorny plants display exceptional
longevity for their size. Based on this it has been proposed that
avoidance of predation selects for a slower aging phenotype.
SUMMARY
The Reproductive-Cell Cycle Theory of Aging is able to
explain:
 Why and how aging occurs in all sexually reproductive life
forms including plants and unicellular organisms.
Reproductive Hormones Drive Aging Via Regulation of
Cell Proliferation and Differentiation
Bonsai Plant (500 years)
Dry climate
 Hostile reproductive environments
such as cold, drought and lack of
light restrict growth and fertility, and
extend longevity.
Mitogens – leaf hormones
 Gibberellins – promotes growth of new leaves, branches and
fruit, lengthens stem; involved in flowering and
fertilization.
 This is artificially achieved with the
Bonsai tree since the cutting of
leaves decreases “caloric intake”
thereby restricting growth and
fertility, and extending longevity.
 Cytokinins – stimulates cell division, promotes growth in
lateral buds, blocks leaf senescence.
Differentiative agents– peripheral hormones
Auxins – promotes growth and elongation towards light,
orients root and shoot growth, inhibits lateral bud
growth, fosters growth of ovary walls for seeds,
prevents abscission of leaves and fruit.
 Ethylene – promotes maturation, fruit ripening and
abscission of leaves, flowers and fruits.
 Abscisic acid – inhibits growth and induces and maintains
dormancy (required during extreme cold and darkness).
The Jomon Cedar on Yakushima
(7200 years old)
Jarrah ( 500 years)
Loss of reproductive function drives senescence
Significant evidence in animals.
“Reproduction is an all-important function of an organism's life
history, and all other vital processes, including senescence
and death, are shaped to serve it.”
Thomas Axenrot
 The simultaneous regulation of the rate of aging and
reproduction.
 How differing rates of reproduction between species is
associated with differences in their lifespan.
 Why fasting extends longevity even though overall caloric
intake is unchanged.
 Two phenomena that are closely related to species lifespan
- the rate of growth and development and the ultimate size of
the animal.
 The apparent paradox that size is directly proportional to
lifespan and inversely proportional to fertility between
species but vice versa within a species.
CONCLUSION
Since reproduction is the most important function of an
organism, if reproductive-cell cycle signaling factors
determine the rate of growth, determine the rate of
development, determine the rate of reproduction, and
determine the rate of senescence, then by definition
they determine the rate of aging and thus lifespan.
Printed for Research ShowCASE by Instructional Technology & Academic Computing (ITAC), 368-3777
Alt. Contact (Last, First):
In summary, we propose that the hormones that regulate reproduction
act in an antagonistic pleiotrophic manner to control aging via cell cycle
signaling; promoting growth and development early in life in order to
achieve reproduction, but later in life, in a futile attempt to maintain
reproduction, become dysregulated and drive senescence.
The leaves act as a sensor of the environment, receiving and
processing information, to appropriately regulate reproductive
function. For example in an environment with plentiful light,
water and nutrients, phytochrome signals for flowering.
Metabolic and Reproductive Cost of Predator Avoidance,
or “Working for Food” Decreases Reproduction and
Extends Longevity
 We propose that some predation avoidance strategies
Dept:
A mechanistic understanding of aging has yet to be described; this
paper puts forth a new theory that has the potential to explain aging in
all sexually reproductive life forms. The theory also puts forth a new
definition of aging - any change in an organism over time. This definition
includes not only the changes associated with the loss of function (i.e.
senescence, the commonly accepted definition of aging), but also the
changes associated with the gain of function (growth and development).
Using this definition, the rate of aging would be synonymous with the
rate of change. The rate of change/aging is most rapid during the fetal
period when organisms develop from a single cell at conception to a
multicellular organism at birth. Therefore, “fetal aging” would be
determined by factors regulating the rate of mitogenesis, differentiation,
and cell death. We suggest these factors also are responsible for
regulating aging throughout life. Thus, whatever controls mitogenesis
and differentiation must also control aging. Since life-extending
modalities consistently affect reproduction, and reproductive hormones
are known to regulate mitogenesis and differentiation, we propose that
aging is primarily regulated by the hormones that control reproduction
(hence, the Reproductive-Cell Cycle Theory of Aging). In mammals,
reproduction is controlled by hypothalamic-pituitary-gonadal (HPG) axis
hormones. Longevity inducing interventions, including caloric
restriction, decrease fertility by suppressing HPG axis hormones and
HPG axis hormones are known to affect signaling through the welldocumented longevity regulating GH/IGF-1/PI3K/Akt/forkhead pathway.
This is exemplified by genetic alterations in C. elegans where
homologues of the HPG axis pathways, as well as the daf-2 and daf-9
pathways, all converge on daf-16, the homologue of human Forkhead
that functions in the regulation of cell cycle events.
Reproductive Friendly vs Reproductive Hostile Environ
Aging Redefined - Change Over Time
Name (Last, First):
ABSTRACT
Email:
Voyager Pharmaceutical Corporation, Raleigh, N.C. and *Department of Medicine, University of Wisconsin, Madison, WI.
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