The Developing Brain
AB_1059
2023
Vrije Universiteit Amsterdam
Maaike Spaans
Module 3/3
Lecture slides, notes from lectures, and notes from Q&A sessions.
Grade: 8.1
1
,INDEX
Most lectures contain slides and notes. Lecture 12-14 (module 3) are notes only. I did not include
notes from the Q&A session in this module, because the questions asked were basic and just
repetition of the earlier course content.
LECTURE 9: BRAIN AGING AND COGNITIVE DECLINE ............................................................................ 3
LECTURE 10: ALZHEIMER’S DISEASE: A CLINICAL APPROACH ............................................................. 23
LECTURE 12: A 100-PLUS STUDY........................................................................................................... 50
LECTURE 13: PARKINSON’S DISEASE .................................................................................................... 54
LECTURE 14: ALZHEIMER’S DISEASE: FUNDAMENTAL MECHANIMS .................................................. 57
2
,LECTURE 9: BRAIN AGING AND COGNITIVE DECLINE
Brain aging
- Like other organs, the brain shows structural and functional (cognitive) decline with age.
- Aging-associated decline in brain function has emerged as a health thread.
- Understanding structural and cognitive decline during normal aging is of critical importance
to understand pathological aging.
- Improve health care in an aging population.
Why do we age and how do we age?
- “It is remarkable that after a seemingly miraculous feat of morphogenesis a complex
metazoan should be unable to perform the much simpler task of merely maintaining what is
already formed” – George C. Williams.
- Why do we age (functional relevance)?
- Evolutionary theories (passive vs active aging).
- How do we age (biological mechanism)?
- Biological theories (somatic mutations/DNA damage, telomeres, mitochondrion/free
radicals, altered proteins and waste accumulation, caloric restriction, sirtuins).
Theories of normal aging
Evolutionary theories of aging
- Passive aging:
- No evolutionary benefit of longer life after reproductive maturity has been reached
→ lifespans evolved relative to reproductive age (fertility).
- Age dependent impairments in maintenance and repair functions.
- Active aging:
- Organisms limit their own lifespan in order to provide evolutionary benefits to the
population (species), such as shifting resources to younger (further evolved)
members.
- A life span management system purposely deactivates maintenance and repair
mechanisms.
- Support:
- Several longevity genes (gerontogenes) exist that affect lifespan and have no
apparent other function.
- Single gene mutations can accelerate aging (Hutchinson-Guilford progeria or
Werner syndrome).
- Against:
- In wild, species rarely survive to ages when senescent deterioration becomes
relevant.
- Not in agreement with “survival of the fittest” theory: anti-aging genes
offering advantage to species should increase among population.
3
, Passive aging (notes):
- Simply not maintaining what has already been formed.
Active aging (notes):
- Actively limiting lifespan. A life span management system that purposely deactivates.
- Some support for this theory: longevity genes (seem only related to aging, no other
functions), gene mutations (accelerate aging).
- Some against:
o Survival of fittest: there should be anti-aging things to battle this aging.
Biological theories of aging
Biological theories of aging – The somatic mutation (DNA damage) theory
- Accumulation of random unrepaired DNA damage results in cellular senescence.
- Support:
- DNA damage-induced aging through cell death may serve to prevent cancer.
Cell death may occur to prevent cancer, but at the cost of aging.
- Human and mouse mutations in DNA repair enzymes result in accelerated
aging phenotypes (Ercc1 gene: Werner syndrome).
Biological theories – somatic mutation (notes):
- Reactive oxygen species (ROS)
- If cell dies, it cannot become tumor (prevention of cancer → hypothesis)
- Support: ERCC1 can accelerate aging. Also seen in mice.
4
AB_1059
2023
Vrije Universiteit Amsterdam
Maaike Spaans
Module 3/3
Lecture slides, notes from lectures, and notes from Q&A sessions.
Grade: 8.1
1
,INDEX
Most lectures contain slides and notes. Lecture 12-14 (module 3) are notes only. I did not include
notes from the Q&A session in this module, because the questions asked were basic and just
repetition of the earlier course content.
LECTURE 9: BRAIN AGING AND COGNITIVE DECLINE ............................................................................ 3
LECTURE 10: ALZHEIMER’S DISEASE: A CLINICAL APPROACH ............................................................. 23
LECTURE 12: A 100-PLUS STUDY........................................................................................................... 50
LECTURE 13: PARKINSON’S DISEASE .................................................................................................... 54
LECTURE 14: ALZHEIMER’S DISEASE: FUNDAMENTAL MECHANIMS .................................................. 57
2
,LECTURE 9: BRAIN AGING AND COGNITIVE DECLINE
Brain aging
- Like other organs, the brain shows structural and functional (cognitive) decline with age.
- Aging-associated decline in brain function has emerged as a health thread.
- Understanding structural and cognitive decline during normal aging is of critical importance
to understand pathological aging.
- Improve health care in an aging population.
Why do we age and how do we age?
- “It is remarkable that after a seemingly miraculous feat of morphogenesis a complex
metazoan should be unable to perform the much simpler task of merely maintaining what is
already formed” – George C. Williams.
- Why do we age (functional relevance)?
- Evolutionary theories (passive vs active aging).
- How do we age (biological mechanism)?
- Biological theories (somatic mutations/DNA damage, telomeres, mitochondrion/free
radicals, altered proteins and waste accumulation, caloric restriction, sirtuins).
Theories of normal aging
Evolutionary theories of aging
- Passive aging:
- No evolutionary benefit of longer life after reproductive maturity has been reached
→ lifespans evolved relative to reproductive age (fertility).
- Age dependent impairments in maintenance and repair functions.
- Active aging:
- Organisms limit their own lifespan in order to provide evolutionary benefits to the
population (species), such as shifting resources to younger (further evolved)
members.
- A life span management system purposely deactivates maintenance and repair
mechanisms.
- Support:
- Several longevity genes (gerontogenes) exist that affect lifespan and have no
apparent other function.
- Single gene mutations can accelerate aging (Hutchinson-Guilford progeria or
Werner syndrome).
- Against:
- In wild, species rarely survive to ages when senescent deterioration becomes
relevant.
- Not in agreement with “survival of the fittest” theory: anti-aging genes
offering advantage to species should increase among population.
3
, Passive aging (notes):
- Simply not maintaining what has already been formed.
Active aging (notes):
- Actively limiting lifespan. A life span management system that purposely deactivates.
- Some support for this theory: longevity genes (seem only related to aging, no other
functions), gene mutations (accelerate aging).
- Some against:
o Survival of fittest: there should be anti-aging things to battle this aging.
Biological theories of aging
Biological theories of aging – The somatic mutation (DNA damage) theory
- Accumulation of random unrepaired DNA damage results in cellular senescence.
- Support:
- DNA damage-induced aging through cell death may serve to prevent cancer.
Cell death may occur to prevent cancer, but at the cost of aging.
- Human and mouse mutations in DNA repair enzymes result in accelerated
aging phenotypes (Ercc1 gene: Werner syndrome).
Biological theories – somatic mutation (notes):
- Reactive oxygen species (ROS)
- If cell dies, it cannot become tumor (prevention of cancer → hypothesis)
- Support: ERCC1 can accelerate aging. Also seen in mice.
4
