cellular aspects of ageing

Question 1

what are the consequences of ageing?

Answer 1

• Reduced tissue/physiological function
• Decreases resistance to stress (both physical and psychological)
• Increases susceptibility to disease (age-related diseases)

Question 2

what are the 2 broad categories of ageing?

Answer 2

cancer

degenerative disease

Question 3

what levels does ageing occur at?

Answer 3

molecules
cells
tissues
organ systems

Question 4

what is cellular ageing a response to?

Answer 4

damage or stress

Question 5

what do tumour suppressor genes do?

Answer 5

cause damaged cells to die or arrest growth (undergo apoptosis or senescence)

Question 6

what are responses to cellular ageing?

Answer 6

cell death (apoptosis) or cell senescence (arrested cell growth)

Question 7

what factors affect life expectancy?

Answer 7

• Disease processes
• Medical treatment
• Lifestyle choices
• Nutrition
• Heredity

Question 8

what are the hallmarks of ageing?

Answer 8

altered intercellular communication
genomic instability
stem cell exhaustion
cellular senescence
mitochondrial dysfunction
deregulated nutrient-sensing
loss of proteostasis
epigenetic alteration
telomere attrition

Question 9

what is the programmed senescence theory?

Answer 9

• Isolated fibroblasts from human tissue and cultured in nutrient media
• Cells divide and form a confluent layer
• Discard half of cells and allow the rest to grow to confluency (= one passage)
• Fibroblast replication slows and stops at ~ 50 passages
• Cells have reached the Hayflick limit and undergone replicative senescence

Question 10

what is the telomeric theory of senescence?

Answer 10

• telomeres shorten with each cell division - when they become too short, the cells enter senescence
• in normal DNA, the ends of the chromosomes arent copied so theres an unreplicated gap. telomerase fills the gap. over time, telomerase levels decrease and telomeres get shorter

Question 11

what are telomeres?

Answer 11

• Telomeres are specialized DNA sequences at the end of chromosomes.
• Non coding repeats of sequence TTA GGG

Question 12

what does telomerase do?

Answer 12

can fill the gap by attaching bases to the end of the chromosomes.
• Enzymes keeps the telomeres logn enough to prevent any important info being lost as they each go through replication

Question 13

what conditions are shortened telomeres found in?

Answer 13

Atherosclerosis, heart disease, hepatitis, cirrhosis

Question 14

what is a free radical?

Answer 14

molecule with unpaired, highly reactive electron

Question 15

how are oxygen free radicals produced?

Answer 15

produced during metabolism or bc of environmental pollution

Question 16

how are reactive oxygen species made?

Answer 16

produced predominantly as a result of electron ‘leak’ during mitochondrial oxidative phosphorylation.

Question 17

what does mitochondrial ageing result in?

Answer 17

increased production of ROS

Question 18

what is the body’s defence system against free radicals?

Answer 18

o Natural antioxidants in the body, such as bilirubin.
o Enzymes such as superoxide dismutase (SOD), catalase, & glutathione peroxidase.
o Dietary antioxidants such as beta carotene, and the vitamins C and E.

Question 19

how do antioxidants deal with free radicals?

Answer 19

Antioxidant has so many electrons in its outer shell that it doesn’t matter too much if it loses one

Question 20

what is autophagy?

Answer 20

an intracellular degradation system that delivers cytoplasmic constituents to the lysosome

Question 21

what does an accumulation of cross linked proteins do?

Answer 21

damages cells and tissue

Question 22

in what conditions are an accumulation of cross linked proteins found?

Answer 22

Alzheimer’s disease

Non-enzymatic glycosylation

Question 23

what happens in Non-enzymatic glycosylation?

Answer 23

occur when glucose molecules attach to proteins causing a chain of chemical reactions resulting in a structural change to the proteins.

Question 24

what are the consequences of non-enzymatic glycosylation reactions?

Answer 24

loss of flexibility of connective tissue (e.g. in arteries – you get cross linking of proteins in the CT of arteries) and microvascular changes in arteries.

Question 25

how does DNA lead to ageing?

Answer 25

an imbalance between rate of DNA repair and accumulation of DNA damage leads to ageing

Question 26

what is nutrient sensing?

Answer 26

a cell’s ability to recognize and respond to fuel substrates like glucose.

Question 27

how does downregulated nutrient sensing occur and how does this lead to disease?

Answer 27

homeostatic mechanisms become disrupted
leads to Reduced insulin sensitivity resulting in glucose intolerance

Increase in visceral fat mass

Question 28

what effect does caloric restriction have on ageing?

Answer 28

prolongs life and improves quality of life

Question 29

what is epigenetics?

Answer 29

factors affecting DNA expression that arent changes in DNA

Question 30

why is there an exhaustion of the stem cell pool?

Answer 30

depletion due to loss of self-renewal and due to senescence

Question 31

what changes in heart function occur during ageing?

Answer 31

• The valves of the heart thicken and become stiffer.
• The number of pacemaker cells decrease. Fatty & fibrous tissues increase about the sinoatrial (SA) node. Slightly slower heart rate.
• The heart wall thickens, so the amount of blood that the chamber can hold may actually decrease.
• The heart may fill more slowly.