aging and disease lecture 1- introduction

Question 1

how is the population aging?

Answer 1

For the first time in history there are now more people over the age of 65 than there are under the age of 5

This gap is only set to widen

Increase in age related diseases

Question 2

what is aging?

Answer 2

Time related deterioration of the physiological functions necessary for fertility and survival

Question 3

what is longevity?

Answer 3

how long an organism lives

Question 4

what is senescence?

Answer 4

time-related deterioration

Question 5

what are development of disease markers?

Answer 5

age related diseases e.g. cancer

Question 6

what is mortality rate?

Answer 6

the probability of death in a given period of time (death rate per year for humans, per month for mice, per day for Drosophila etc.)

Question 7

what are semelparity?

Answer 7

genetically programmed senility and death after reproducing

Question 8

Is aging a random process in multi-cellular organisms?

Answer 8

If the mortality rate of Drosophila was constant, the survival graph would look like a direct line which might happen if death was a random process – like the probability of being eaten by a predator. A bird eating the fly.

Question 9

what is the survivorship curve?

Answer 9

its actually curved and there are dips and rises in the curve

Question 10

what are the 4 mortality phases?

Answer 10

-Raised mortality in infancy.
-Low mortality until mid-life (~60 years of age)
-High mortality mid-life to old age.
-Reduced mortality in extreme old age (relative to old age).

Question 11

what is Alzheimers?

Answer 11

Alzheimer’s is the most common form of dementia

Question 12

what does the naked mole rat show?

Answer 12

Naked mole rat: unusual physiology, can survive ~20 mins without oxygen, rarely get cancer, high levels of DNA repair and chaperones to maintain correct protein folding. Age-specific mortality does not increase with age – even at ages 25-fold past reproductive maturity.

Theyrarely get cancer, are resistant to some types of pain, and cansurvive up to 18 minutes without oxygen. But perhaps their greatest feat, a new paper suggests, is that they don’t age.

Question 13

what are genetic linkage studies?

Answer 13

diseases of premature aging - Monogenic, causal

Question 14

what is GWAS?

Answer 14

complex trait, many SNPs, low effect size
Still early days!!
Multi- trait loci have been linked with several age- related diseases, suggesting shared ageing influences (Meltzer et al. 2020 Nature).
TCF7L2 (T2D) also linked to lifespan

Question 15

what are progeroid syndromes?

Answer 15

constitute a group of genetic disorders characterized by clinical features mimicking physiological aging at an early age.

Question 16

what is segmental progeria?

Answer 16

Werner syndrome (gene: WRN)
Cockayne syndrome (gene: ERCC6)
Multiple tissues affected
Autosomal recessive

Question 17

what are unimodal progeroid syndromes?

Answer 17

Familial Alzheimer’s Disease (gene: APP)
Familial Parkinson’s Disease (gene: SNCA)
One main tissue affected
Autosomal dominant

Question 18

what is the most common feature of accelerated aging in progeroid syndromes?

Answer 18

the loss of genome integrity

Question 19

is there a similarity between molecule hallmarks of aged cells and progeroid syndromes

Answer 19

Similarities between molecular hallmarks of aged cells and the human progeroid syndromes are remarkable.

Question 20

does human progeroid syndromes accelerate aging processes?

Answer 20

yes, there is a very powerful argument that the molecular defects caused by these syndromes are major causative agents of ageing.

Question 21

what is the age machine?

Answer 21

The hallmarks of aging

Interconnected processes

Direct impact on the development of age related diseases

Question 22

what are types of hallmarks?

Answer 22

primary = causes of damage
antagonistic= responses to damage
integrative= culprits of the phenotype