Aging Brain

Question 1

Why can’t evolution select for or against aging diseases?

Answer 1

There are hardly ever aging individuals in wild populations and thus no individuals on which natural selection can act upon

Question 2

Do genes affect longevity?

Answer 2

Yes. This has been shown in C. elegans, fruitfly, mice, and some human centenarians.

These genes are involved e.g., in metabolic consumption regulation, defending and repairing cellular damage rising from oxidative metabolism.

Question 3

How does macromolecular damage work with aging?

Answer 3

The accumulation of macromolecular damage is stochastic.

Aging rate/disease is determined by the balance between damage accumulation and repair.

Question 4

What is the disposable soma theory?

Answer 4

• Primary cause of aging is stochastic accumulation of cellular and molecular damage, arising from evolved limitations in somatic maintenance and repair functions
• There’s an optimal balance of energy for each species between maintenance and reproduction
• Individual aging rate determined by the balance between stochastic damage accumulation and repair rate

Question 5

What is the reproduction and longevity aspect of disposable soma theory?

Answer 5

• There is a trade off between longevity and fertility. Longer life means reduced fertility.
• Study among 33.000 British aristocrats showed that long living females never breed or breed few and at a late age

Question 6

How does the reproduction and longevity aspect of disposable soma theory affect mice?

Answer 6

• 90%+ of mice in the wild die within the first year of various unpredictable causes
• Investment of energy into repair would be a loss, and eliminated by Darwinian selection
• Instead, mice ‘invest’ into thermogenesis and reproduction rather than repair and maintenance

Question 7

How do premature aging diseases work in humans?

Answer 7

• Virtually all are due to defects in DNA metabolism and repair -> suggests that this is critical in aging regulation

Question 8

How does macromolecular damage, that accumulates stochastically, affect the brain, when it comes to failure of repairing or degrading of proteins?

Answer 8

• Most common neurodegenerative diseases, AD and PD, involve failure of cleaning up damaged or wrongly folded proteins, mitochondrial dysfunction, axonal transport failure
• In PD, 90% + have Lewy bodies with accumulated alpha-synuclein