CONCEPTS AND THEORIES OF
HEALTHY AGING
NEM-52306
,Lecture 1: Theories and evolution of aging
Topics & learning goals
• Aging is a unique problem
o Be able to define aging
• Identifying the main questions
o Understand how the complexity of aging emerges from theory
o Explain the potential relationships between aging, health and disease
• Evolutionary theories of aging
o Understand how environmental mortality leads to the evolution of aging
• From theory to experiments
o Explain how the decreasing power of natural selection with age relates to the
genetics of aging
Aging, a unique problem
Aging: the total effect of those intrinsic changes that accumulate in the course of life that
negatively affect the vitality of the organism, and that makes it more susceptible to the
factors that can cause death
- Established using demographic data from cohorts of organisms. Hard to measure in
individuals
Statistical definition: mortality is the sum of intrinsic and extrinsic factors
- No aging: mortality rate does not change
- Aging: mortality rate accelerates with age (time)
,Environmental mortality should be reduced as much as possible to measure aging (=intrinsic
mortality).
Decreasing environmental mortality reveals ageing in humans
o The me is decreased in 1980 compared to 1800
Increased survival when environmental mortality decreases
Aging in nature is rare, as extrinsic mortality dominates
Aging becomes visible when extrinsic mortality is
(largely) removed
o E.g. laboratory conditions
Aging is largely a unique human problem in natural
environments
o Humans can show the effects and extend of
aging
Aging is complex:
- Affects many ‘systems’
- Intrinsic factors
- Gradual process
- Accumulation of damage
,What explains variation in lifespan and aging?
Extrinsic mortality
o 30-year-old people in 1750 had the same mortality rate as 72-year-old people
now
o Mortality improvement is on par with or greater than the reduction in
mortality in other species achieved by laboratory selection experiments and
endocrine pathway mutations.
Increase achieved by environmental changes
Variation in lifespan and ageing is still there
Identifying the main questions
Why do we age?
Aging limits the reproductive potential of an individual and should as such be opposed by
natural selection.
Is aging beneficial?
→ No
Why is the integrity of the soma (body cells) not maintained?
What explains variation in lifespan?
- High between-organism variation
- Low within-organism variation
→ Genetic component
What are the factors that influence aging?
• Stochasticity: damage to DNA, cells and tissues as a by-product
of metabolism
o Random variable, accumulate over time
• Environment
• Genetics
o Lifespan within species is fairly uniform
o Genetic alterations can be associated with premature
aging syndromes/phenotypes
What is the relationship between disease and aging?
Accumulation of damage (aging) diminishes the capacity to maintain homeostasis under
stressful environments, leading to a greater risk for many diseases
Age-related diseases
o Cancer, CVD, neurodegenerative disorders
However, aging does not have to be the cause of specific disease
Cell-senescence: consequence of exposure to intrinsic and extrinsic aging factors,
characterized by gradual accumulation of DNA damage leading to altered cell
function
, Is aging a programmed process?
Genetics can play a role in programmed aging, but stochasticity also plays a role.
Accumulation of damage contributes to increased mortality rates
Stochasticity Versus Genetics
- Accumulation of damage, - Genetic control
- Stochastic - Variation
- Irreversible - Death rate reversible
Evolutionary theories of aging
Evolution theories predict when aging will or will not evolve.
- Critical condition of evolution of aging: distinct parents and offspring
Key traits for evolution: reproduction and survival
Determine the strength/intensity of natural selection
o Survival and reproduction decrease with time
o Intensity = survival + reproduction
HEALTHY AGING
NEM-52306
,Lecture 1: Theories and evolution of aging
Topics & learning goals
• Aging is a unique problem
o Be able to define aging
• Identifying the main questions
o Understand how the complexity of aging emerges from theory
o Explain the potential relationships between aging, health and disease
• Evolutionary theories of aging
o Understand how environmental mortality leads to the evolution of aging
• From theory to experiments
o Explain how the decreasing power of natural selection with age relates to the
genetics of aging
Aging, a unique problem
Aging: the total effect of those intrinsic changes that accumulate in the course of life that
negatively affect the vitality of the organism, and that makes it more susceptible to the
factors that can cause death
- Established using demographic data from cohorts of organisms. Hard to measure in
individuals
Statistical definition: mortality is the sum of intrinsic and extrinsic factors
- No aging: mortality rate does not change
- Aging: mortality rate accelerates with age (time)
,Environmental mortality should be reduced as much as possible to measure aging (=intrinsic
mortality).
Decreasing environmental mortality reveals ageing in humans
o The me is decreased in 1980 compared to 1800
Increased survival when environmental mortality decreases
Aging in nature is rare, as extrinsic mortality dominates
Aging becomes visible when extrinsic mortality is
(largely) removed
o E.g. laboratory conditions
Aging is largely a unique human problem in natural
environments
o Humans can show the effects and extend of
aging
Aging is complex:
- Affects many ‘systems’
- Intrinsic factors
- Gradual process
- Accumulation of damage
,What explains variation in lifespan and aging?
Extrinsic mortality
o 30-year-old people in 1750 had the same mortality rate as 72-year-old people
now
o Mortality improvement is on par with or greater than the reduction in
mortality in other species achieved by laboratory selection experiments and
endocrine pathway mutations.
Increase achieved by environmental changes
Variation in lifespan and ageing is still there
Identifying the main questions
Why do we age?
Aging limits the reproductive potential of an individual and should as such be opposed by
natural selection.
Is aging beneficial?
→ No
Why is the integrity of the soma (body cells) not maintained?
What explains variation in lifespan?
- High between-organism variation
- Low within-organism variation
→ Genetic component
What are the factors that influence aging?
• Stochasticity: damage to DNA, cells and tissues as a by-product
of metabolism
o Random variable, accumulate over time
• Environment
• Genetics
o Lifespan within species is fairly uniform
o Genetic alterations can be associated with premature
aging syndromes/phenotypes
What is the relationship between disease and aging?
Accumulation of damage (aging) diminishes the capacity to maintain homeostasis under
stressful environments, leading to a greater risk for many diseases
Age-related diseases
o Cancer, CVD, neurodegenerative disorders
However, aging does not have to be the cause of specific disease
Cell-senescence: consequence of exposure to intrinsic and extrinsic aging factors,
characterized by gradual accumulation of DNA damage leading to altered cell
function
, Is aging a programmed process?
Genetics can play a role in programmed aging, but stochasticity also plays a role.
Accumulation of damage contributes to increased mortality rates
Stochasticity Versus Genetics
- Accumulation of damage, - Genetic control
- Stochastic - Variation
- Irreversible - Death rate reversible
Evolutionary theories of aging
Evolution theories predict when aging will or will not evolve.
- Critical condition of evolution of aging: distinct parents and offspring
Key traits for evolution: reproduction and survival
Determine the strength/intensity of natural selection
o Survival and reproduction decrease with time
o Intensity = survival + reproduction
