Nutrition and the ageing body
Lecture 1/2:
Lifespan: LE is increasing but briefly decreased due to covid
LE is different per ethnic group
Is there a maximum lifespan?
Healthspan: years spend in good health > loss: CVD, diabetes, cancer, dementia
(lifestyle vs genetics). Gap between lifespan and healthspan increases (large
difference between socioeconomic classes)
Effect lifestyle on lifespan: smoking, PA, alcohol, diabetes, BMI, hypertension
Genetics: long-lived siblings, parents, partners increases chance to reach high
age.
Partners: traits, behaviour, environment
Genetics explains max 25% of differences APOE & FOXA3A, sometimes genes do
have dramatic effects
Evolution of ageing:
Essential lifespan: survival of body until reproduction
No evolutionary advantage to ageing
Death will occur before old age
Ageing is result of absence of natural selection pressures or deleterious effects at
later age of genes with advantageous effects during development
Menopause:
1. Adaptive: selective advantage of female reproductive cessation, more
energy into helping existing children instead of having more
2. Nonadaptive: artifact of the dramatic increase in human life expectancy,
non-existent in other mammals except for whales
Grandmother hypothesis: stay healthy to care for grandchildren
Lecture 3:
What is ageing?
Ageing is the process during which structural and functional changes accumulate
in an organism as a result of the passage of time. The changes manifest as a
decline from the organisms peak fertility and physiological functions until death.
(starts between 30-40y)
1. Accumulation of damage: inevitable (metabolism, DNA damage, genetic
predispositions), preventable (exposure to toxins, sunlight, alcohol,
smoking, radioactivity)
2. Antagonistic pleiotropy: certain genes are beneficial in development but
harmful later in life (mTOR, autophagy)
, 3. Disposable soma: energy either goes into growth and reproduction OR anti-
ageing and repair.
Caloric restriction increases lifespan
Hallmarks of ageing should include:
1. Should manifest during normal ageing
2. Its experimental aggravation should accelerate ageing
3. Its experimental amelioration should retard the ageing process and thus
increase healthy lifespan
1. Loss of proteostasis (protein misfolding)
a. Stress causes protein to unfold, these should be refolded or be
disposed of, if not aggregation happens
b. Autophagy: enzyme eats the misfolded proteins (larger proteins,
under stress conditions)
c. Ubiquitin-proteosomal degradation: proteins are shredded (smaller
proteins, always running)
d. Heat shock proteins: can refold misfolded proteins, increased
expression could be carcinogenic. Respond to stressors such as
heat, cold, UV-light, exercise, alcohol and fasting and some
nutrients: glutamine, pre-/probiotics, restriction
2. Disabled autophagy
a. Mainly involves macroautophagy
b. Expression of autophagy-related genes declines with age
c. Decreased autophagy = increased ageing
d. Caloric restriction and intermittent fasting
3. Genomic instability
a. Ageing = accumulation of genetic damage throughout life
b. Increased DNA damage accumulation can cause Werner syndrome>
premature ageing
c. Sources of DNA damage:
i. Endogenous: metabolism (ROS production> antioxidants),
replication (DNA polymerase)
ii. Exogenous: UV light, radiation, smoking, air pollution
4. Telomere attrition
a. Telomeres shorten per reproduction cycle until they reach replicative
senescence (after 40-60 replications) (Hayflick limit)
b. Telomerase increases telomere length, but is not expressed in many
cells (may be carcinogenic)
c. Telomere length is not a better predictor of mortality than
chronological age
5. Chronic inflammation
a. Inflammaging: due to several factors (hormones, cellular debris)
dysregulating intracellular homeostasis, secretion of cytokines are
increased
b. Immunosenescence: age-related impairments in innate and adaptive
immune system (impaired immune response)
6. Altered intracellular communication
Lecture 1/2:
Lifespan: LE is increasing but briefly decreased due to covid
LE is different per ethnic group
Is there a maximum lifespan?
Healthspan: years spend in good health > loss: CVD, diabetes, cancer, dementia
(lifestyle vs genetics). Gap between lifespan and healthspan increases (large
difference between socioeconomic classes)
Effect lifestyle on lifespan: smoking, PA, alcohol, diabetes, BMI, hypertension
Genetics: long-lived siblings, parents, partners increases chance to reach high
age.
Partners: traits, behaviour, environment
Genetics explains max 25% of differences APOE & FOXA3A, sometimes genes do
have dramatic effects
Evolution of ageing:
Essential lifespan: survival of body until reproduction
No evolutionary advantage to ageing
Death will occur before old age
Ageing is result of absence of natural selection pressures or deleterious effects at
later age of genes with advantageous effects during development
Menopause:
1. Adaptive: selective advantage of female reproductive cessation, more
energy into helping existing children instead of having more
2. Nonadaptive: artifact of the dramatic increase in human life expectancy,
non-existent in other mammals except for whales
Grandmother hypothesis: stay healthy to care for grandchildren
Lecture 3:
What is ageing?
Ageing is the process during which structural and functional changes accumulate
in an organism as a result of the passage of time. The changes manifest as a
decline from the organisms peak fertility and physiological functions until death.
(starts between 30-40y)
1. Accumulation of damage: inevitable (metabolism, DNA damage, genetic
predispositions), preventable (exposure to toxins, sunlight, alcohol,
smoking, radioactivity)
2. Antagonistic pleiotropy: certain genes are beneficial in development but
harmful later in life (mTOR, autophagy)
, 3. Disposable soma: energy either goes into growth and reproduction OR anti-
ageing and repair.
Caloric restriction increases lifespan
Hallmarks of ageing should include:
1. Should manifest during normal ageing
2. Its experimental aggravation should accelerate ageing
3. Its experimental amelioration should retard the ageing process and thus
increase healthy lifespan
1. Loss of proteostasis (protein misfolding)
a. Stress causes protein to unfold, these should be refolded or be
disposed of, if not aggregation happens
b. Autophagy: enzyme eats the misfolded proteins (larger proteins,
under stress conditions)
c. Ubiquitin-proteosomal degradation: proteins are shredded (smaller
proteins, always running)
d. Heat shock proteins: can refold misfolded proteins, increased
expression could be carcinogenic. Respond to stressors such as
heat, cold, UV-light, exercise, alcohol and fasting and some
nutrients: glutamine, pre-/probiotics, restriction
2. Disabled autophagy
a. Mainly involves macroautophagy
b. Expression of autophagy-related genes declines with age
c. Decreased autophagy = increased ageing
d. Caloric restriction and intermittent fasting
3. Genomic instability
a. Ageing = accumulation of genetic damage throughout life
b. Increased DNA damage accumulation can cause Werner syndrome>
premature ageing
c. Sources of DNA damage:
i. Endogenous: metabolism (ROS production> antioxidants),
replication (DNA polymerase)
ii. Exogenous: UV light, radiation, smoking, air pollution
4. Telomere attrition
a. Telomeres shorten per reproduction cycle until they reach replicative
senescence (after 40-60 replications) (Hayflick limit)
b. Telomerase increases telomere length, but is not expressed in many
cells (may be carcinogenic)
c. Telomere length is not a better predictor of mortality than
chronological age
5. Chronic inflammation
a. Inflammaging: due to several factors (hormones, cellular debris)
dysregulating intracellular homeostasis, secretion of cytokines are
increased
b. Immunosenescence: age-related impairments in innate and adaptive
immune system (impaired immune response)
6. Altered intracellular communication
