Lecture 24 The evolution of ageing
Ageing are progressive physiological changes in an organism over time that result in a decrease in
intrinsic ability to survive and reproduce, and an increase in health problems. For a population to have
good survival, there is no need to evolve impossibly perfect molecular maintenance mechanisms: an
immortal germline & disposable soma. No organism lives forever, but there are large variations in
lifespans between and within species. Also, there are large variations in age-related health problems.
Life history theory explains inter- and intraspecific variation in the characteristics of the life cycle:
longevity, development time, age at reproduction, body size, number of offspring. Internal mortality are
factors from inside the body, such as cancer or metabolic, cardiovascular or neurodegenerative diseases.
External mortality are factors that come from outside, such as predation, infection, starvation,
dehydration, freezing, etc. Population with a high extrinsic mortality tend to have an early maturation,
increased fecundity, less investment in maintenance and a shorter intrinsic lifespan. There are changes
in the extrinsic mortality in the human history (transition from hunter-gatherer to agriculture or the
industrial revolution).
Resource acquisition and allocation are principle of the life
history evolution. It is called the Y-model. This model is saying
that correlate responses can’t just be explained by having a
limited set of resources and that there has to be decisions by
an organism on how to use these resources. This results in
trade-off. A trade-off is something that is beneficial for one
trade or one phenotype and it is going to have negative effects
on another phenotype.
The first evolutionary theory of ageing stems from the
idea of selection shadow. The selection acts on
reproduction and because reproduction will slowly
decrease, its force would be reduced with H. The force
of selection is on the y-axis and H is on the x-axis. The
first linear part is the maturation. The selection is
strong, to make sure you mature well. Once the age of
maturity is reached, an organism will start to
reproduce. Most organisms reproduce a lot at first,
but then reproduction decreases. Because this
decreases, the selective force is also decreasing.
The second theory is the mutation accumulation
theory. It states that weak selection at increased ages is insufficient to remove deleterious mutations
from the population. Because if these diseases are only manifested later on in life, there is not so much
selective pressure on it anymore. Mutations that act
like this would sort of accumulate in a population.
This results in much less deaths in younger people
and a lot of people reach the maximum age. This
happens typically with late-onset diseases, such as
Huntington disease.
Williams came up with the idea of antagonistic
pleiotropy. He proposed that aging can evolve
because a genetic or physiological mechanism has a
, positive effect on one trait, but a negative effect on another trait. This is
the result of evolutionary tinkering. Examples of antagonistic pleiotropy is
the endocrine system, which regulates most physiological functions:
IIS/TOR, testosterone, leptin. This theory suggest that this is the reason for
trade-off between lifespan and reproduction. Antagonist pleiotropy has
beneficial early-life effects, but deleterious late-life effects.
Antagonist pleiotropy led to 2 other theories: “disposable soma” and the
developmental theory of ageing.
The disposable soma theory is about organisms have to balance energy invested in reproduction with
DNA repair mechanisms (ageing). The processes that are involved in growth and reproduction require
energy and causes cellular damage. Somatic cells are maintained only to ensure reproduction and
afterwards, the soma is disposable. Then, it doesn’t matter if cells are being damaged, it only matters if
you can’t produce before that time. The question is: what is the optimal amount of repair that you need
to achieve the maximum fitness? There needs to be a certain amount of repair, otherwise you wouldn’t
survive development.
The developmental theory of ageing says that gene expression is optimized to have the best possible
development and early life for reproduction. As you age, the genes are still there and they will be
expressed, but there is a suboptimal for this. This theory says that it is possible to change expression
levels of a gene to increase the lifespan and it would not have a cost at reproduction.
Rapamycin supplements extend the lifespan in mice. But it has a mixed effect on ageing phenotypes. It
has a positive effect on cancer incidence, memory, body composition and no effect on muscle function,
vision, heart pathology, DNA damage. Ageing is a by-product of many physiological mechanisms and
processes. It is a highly polygenic trait, with many proximate causes. When you treat one cause or
problem, other problems will emerge. There is a large effect of environmental factors: heritability 15-
30%.
Lecture 25 Journal club: gut pathology
Sex and gender have an effect on modifiers of morphology, metabolism, physiology, health and disease.
Male-female difference also has an impact on treatment efficiency and diagnosis. Sex-specific
differences are mostly overlooked until recently with detrimental effects on female health. It is the
result of differences in reproduction. The gut is important for reproduction. The gut plays a critical role
in nutrient uptake and, therefore, in the availability of resources for life history traits. Female
reproduction is energetically very costly, requiring female adaptations. Female reproduction is
associated with gut remodeling in fruit flies and mammalian species. The
gut causes changes in morphology, physiology, metabolism and gene
expression. It is mediated by endocrine signaling.
Dietary restriction is the moderate reduction of food intake (caloric
restriction or restricting specific amino acids) without inducing malnutrition.
In humans, 75% of weight maintenance requires energy, so for dietary
restriction, this means to cut your calorie intake with 25%. This promotes
healthy aging and longevity. It also results in a reduction in reproduction. It
is an adaptation to promote survival until higher nutrient is available.
A couple of facts used in this study are:
Women live longer than men in modern society, but suffer from higher levels of morbidity later
in life
Ageing are progressive physiological changes in an organism over time that result in a decrease in
intrinsic ability to survive and reproduce, and an increase in health problems. For a population to have
good survival, there is no need to evolve impossibly perfect molecular maintenance mechanisms: an
immortal germline & disposable soma. No organism lives forever, but there are large variations in
lifespans between and within species. Also, there are large variations in age-related health problems.
Life history theory explains inter- and intraspecific variation in the characteristics of the life cycle:
longevity, development time, age at reproduction, body size, number of offspring. Internal mortality are
factors from inside the body, such as cancer or metabolic, cardiovascular or neurodegenerative diseases.
External mortality are factors that come from outside, such as predation, infection, starvation,
dehydration, freezing, etc. Population with a high extrinsic mortality tend to have an early maturation,
increased fecundity, less investment in maintenance and a shorter intrinsic lifespan. There are changes
in the extrinsic mortality in the human history (transition from hunter-gatherer to agriculture or the
industrial revolution).
Resource acquisition and allocation are principle of the life
history evolution. It is called the Y-model. This model is saying
that correlate responses can’t just be explained by having a
limited set of resources and that there has to be decisions by
an organism on how to use these resources. This results in
trade-off. A trade-off is something that is beneficial for one
trade or one phenotype and it is going to have negative effects
on another phenotype.
The first evolutionary theory of ageing stems from the
idea of selection shadow. The selection acts on
reproduction and because reproduction will slowly
decrease, its force would be reduced with H. The force
of selection is on the y-axis and H is on the x-axis. The
first linear part is the maturation. The selection is
strong, to make sure you mature well. Once the age of
maturity is reached, an organism will start to
reproduce. Most organisms reproduce a lot at first,
but then reproduction decreases. Because this
decreases, the selective force is also decreasing.
The second theory is the mutation accumulation
theory. It states that weak selection at increased ages is insufficient to remove deleterious mutations
from the population. Because if these diseases are only manifested later on in life, there is not so much
selective pressure on it anymore. Mutations that act
like this would sort of accumulate in a population.
This results in much less deaths in younger people
and a lot of people reach the maximum age. This
happens typically with late-onset diseases, such as
Huntington disease.
Williams came up with the idea of antagonistic
pleiotropy. He proposed that aging can evolve
because a genetic or physiological mechanism has a
, positive effect on one trait, but a negative effect on another trait. This is
the result of evolutionary tinkering. Examples of antagonistic pleiotropy is
the endocrine system, which regulates most physiological functions:
IIS/TOR, testosterone, leptin. This theory suggest that this is the reason for
trade-off between lifespan and reproduction. Antagonist pleiotropy has
beneficial early-life effects, but deleterious late-life effects.
Antagonist pleiotropy led to 2 other theories: “disposable soma” and the
developmental theory of ageing.
The disposable soma theory is about organisms have to balance energy invested in reproduction with
DNA repair mechanisms (ageing). The processes that are involved in growth and reproduction require
energy and causes cellular damage. Somatic cells are maintained only to ensure reproduction and
afterwards, the soma is disposable. Then, it doesn’t matter if cells are being damaged, it only matters if
you can’t produce before that time. The question is: what is the optimal amount of repair that you need
to achieve the maximum fitness? There needs to be a certain amount of repair, otherwise you wouldn’t
survive development.
The developmental theory of ageing says that gene expression is optimized to have the best possible
development and early life for reproduction. As you age, the genes are still there and they will be
expressed, but there is a suboptimal for this. This theory says that it is possible to change expression
levels of a gene to increase the lifespan and it would not have a cost at reproduction.
Rapamycin supplements extend the lifespan in mice. But it has a mixed effect on ageing phenotypes. It
has a positive effect on cancer incidence, memory, body composition and no effect on muscle function,
vision, heart pathology, DNA damage. Ageing is a by-product of many physiological mechanisms and
processes. It is a highly polygenic trait, with many proximate causes. When you treat one cause or
problem, other problems will emerge. There is a large effect of environmental factors: heritability 15-
30%.
Lecture 25 Journal club: gut pathology
Sex and gender have an effect on modifiers of morphology, metabolism, physiology, health and disease.
Male-female difference also has an impact on treatment efficiency and diagnosis. Sex-specific
differences are mostly overlooked until recently with detrimental effects on female health. It is the
result of differences in reproduction. The gut is important for reproduction. The gut plays a critical role
in nutrient uptake and, therefore, in the availability of resources for life history traits. Female
reproduction is energetically very costly, requiring female adaptations. Female reproduction is
associated with gut remodeling in fruit flies and mammalian species. The
gut causes changes in morphology, physiology, metabolism and gene
expression. It is mediated by endocrine signaling.
Dietary restriction is the moderate reduction of food intake (caloric
restriction or restricting specific amino acids) without inducing malnutrition.
In humans, 75% of weight maintenance requires energy, so for dietary
restriction, this means to cut your calorie intake with 25%. This promotes
healthy aging and longevity. It also results in a reduction in reproduction. It
is an adaptation to promote survival until higher nutrient is available.
A couple of facts used in this study are:
Women live longer than men in modern society, but suffer from higher levels of morbidity later
in life
