Case 25 - Biology Of Ageing

Front 1

Late acting gene theory

Back 1

Ageing caused by gene mutations that cannot be selected out.
eg Huntington's, apoliprotein A4

Front 2

Antagonistic Pleiotropy

Back 2

Genes beneficial in early life are harmful later:
eg. sickle trait early:anti-malarial.
late: haemorrhage, organ failure

Front 3

Disposable soma theory

Back 3

Effective cell maintenance and repair costly.
Soma (body) cells are sacrificed to maintain germ cells.

Front 4

Reactive Oxygen Species

Back 4

Intrinsic Damage from electron leak through ETC.
Mutations in ETC can lead to worse damage and shorter lifespan.
ROS affect all molecules.
Damage to mitochondria can cause cell death by apoptosis or necrosis.

Front 5

Protection against ROS

Back 5

Intrinsic: Superoxide Dismutase
Good correlation between activity and lifespan.
Non-enzyme antioxidants: less effective, one ROS per molecule.
Vitamin studies in human very inconclusive, possibly damaging.

Front 6

Malliard Reaction

Back 6

Spontaneous chemical reaction between proteins and sugars.
Leads to the formation of A.G.E.s
AGE increase exponentially with age.
Increases in AGEs are earlier in diabetes.

Front 7

Telomeres

Back 7

Telomeres: prevent fusion breakage fusion cycles.
1) cap chromosomes.
2) Buffer sequence loss to end replication problem.
3) Block mortal cell growth in response to DNA damage and mutation risk
Telomerase counteracts telomere shortening in immortal cells.
Senescence is triggered at a strain specific telomere length.
Senescence is very similar to a DNA damage pathway.

Front 8

Is senescence only about telomeres?

Back 8

Oxidative stress and ROS damage telomeres.
Cell senescence is a continuous feedback loop between DNA damage and mitochondrial dysfunction, controlled by p53.

Front 9

consequences of mtDNA mutation

Back 9

Mitochondria increase in size.
Do not divide.
Increased production of hydrogen peroxide damages mitochondrial membranes.
ETC stops working and ROS transferred outside cell.
Damage spreads.

Front 10

Diabetes damage

Back 10

1)Hyperinsulinaemia causes Neurodegeneration.
2)Hyperglycaemia leads to vasoconstriction through reduced NO production.
3) Hyperglycaemia leads to more AGE. Modifies RBC, wrinkles skin, stiffens arteries.

Front 11

Endocrine Changes and Ageing

Back 11

GH:14 % decrease year on year.
Leads to many emotional and pyschological problems.
Cortisol: Raised cortisol leads to long term elevated glucocorticoids = neuronal loss.
neuronal loss= decreased inhibition of hypothalamus

Age related changes in hormonal rhythms, body core temp, sleep-wakefullness etc.

Front 12

Reproduction and Ageing: Male

Back 12

Decreasing Testosterone in ageing leads to poor functioning spermatozoa.
Risk of miscarriage and genetic abnormalities increases with parental age.
The large number of mitotic divisions increases chances of accumulating gene defects.

Front 13

Reproduction and Ageing: Female

Back 13

Age related decline in oocyte numbers in human ovaries.
Also, decline in fertility before the menopause. Ageing eggs.
Menopause: decreased DHEA. Increasing DHEA can reverse some of hte effects of the menopause.

Front 14

Bone Ageing and Osteoporosis

Back 14

At any age: Lack of mechanical stress.
Osteoporosis:
1) Decline in sex hormones. decreased oestrogen = increased osteoclast activity.
2) Increased TNFa leads to increased numbers of oesteoclast precursors.
3) Poor calcium homeostasis.
other ageing factors, gut, kidney. Bones sacrificed to maintain Ca2+ concentration.
4)Osteoblast senescence.