The cellular aspects of ageing

Question 1

what is ageing

Answer 1

• Gradual and spontaneous changes occur in maturation from infant to adulthood, these changes underpin a normal physiological decline seen in middle and late adulthood

Question 2

ageing is a

Answer 2

• Ageing is a biological process not a disease

Question 3

what are the consequences of ageing

Answer 3

• Reduce tissue and physiological function
• Decreased resistance to stress – physical and psychological
• Increased susceptibility to disease

Question 4

what are the two broad categories of ageing

Answer 4

cancer and degenerative disease

Question 5

what are the degenerative diseases of ageing

Answer 5

Alzheimer’s, kidneys disease, heart disease, autoimmune disease, cogntivie decline

Question 6

what levels does ageing occur at

Answer 6

• Molecules
• Cell
• Tissues
• Organs

Question 7

how do cells respond to damage or stress

Answer 7

Cells respond to damage or stress via cell death (apoptosis) and arrested cell growth (cell senescence)

Question 8

what are factors that influence life expectancy

Answer 8

• Disease Processes
• Medical Treatment
• Lifestyle Choices
• Nutrition
• Heredity

Question 9

what is tumour suppression genes

Answer 9

• these are genes that have evolved to protect from cancer, they can cause the damage cells to die or arrest growth

Question 10

How do you use genes to study ageing

Answer 10

• Classic genetic approach

- Isolate and study mutants with altered ageing

Question 11

what are the hallmarks of ageing

Answer 11

• Telomere attrition
• Cellular senescene
• Mitochondrial dysfunction
• Deregulated nutrient sensing
• Loss of proteostatsis
• Epigenic alterations
• Genomic instability
• Stem cell exhaustion
• Altered intracellular communication

Question 12

what does ageing result from

Answer 12

• Cell intrinsic factors

- Cell extrinsic factors

Question 13

what does the hay flick limit prove

Answer 13

cell senscene theory

Question 14

describe how the hay flick limit works

Answer 14

• They isolated fibroblasts from human tissue and put it in a cultred nutrient media
• Cells divide and form a confluent layer
• Discard half of cells and allow the rest to grow confluency
• Fibroblast replication slows and stops at 50 passages
• Cell have reached the hayflick limit and undergo replicative senescene

Question 15

describe the action of telomerase in normal DNA replication

Answer 15

• End of the chromosome is not cpopeid exactly which leaves an unreplicated gap
• The enzyme telomerase filsl the gap by attaching bases to the end of the chromosome to exnted it and make it longer again
• Telomerase keeps the telmoers longer to prevent information from being lost
• Over time tleomerase levels decrease and the telmoers become hsorter and shorter

Question 16

describe the telomeric theory of senescene

Answer 16

• This is an extension of the hayflick limit
• Telomeres are specialised DNA sequences at the end of the chromosomes
• Non coding repeat of sequences TTA GGG
• Telomeres shorten with each cell division
• When the telomeres become too short the cells enters senescence

Question 17

where are shortened telomeres found

Answer 17

– Atherosclerosis
– Heart disease
– Hepatitis
– Cirrhosis

Question 18

describe how telomeric theory link to cancer

Answer 18

• 90% of cancer cells have been found to possess telomerase.
– Telomerase prevents the telomere from shortening.
– This allows the cancer cells to reproduce, resulting in tumor growth.
– Balancing act between cellular ageing and cancer

Question 19

how does alternated intracellular communication lead to ageing

Answer 19

• Signals between cells change over ageing
• Biological clocks act through hormones to control the pace of ageing
• The hormones affect growth, methabolism, temperature, inflammation and stress
• For example menopause

Question 20

How does the immune system decline lead to ageing

Answer 20

• A programmed decline in the immune system leads to an increased vulnerability to disease, ageing and death
• Decrease in thymus dependent immunity and the hormones that are secreted by the thymus

Question 21

what is a free radical

Answer 21

• A free radical is a molecule with an unpaired, highly reactive electron

Question 22

what does a free radical do to cells and organs

Answer 22

• During aging, damage produced by free radicals causes cells and organs to stop functioning.

Question 23

name a type of free radical

Answer 23

• One type of very reactive free radical is the oxygen free radical, which may be produced during metabolism or as a result of environmental pollution.

Question 24

how do mitochondria cause free radical damage

Answer 24

Mitochondria – get electron leaks, these generate free radicals, they cause damage and it carry’s on and on
Reactive oxygen species (ROS) are produced predominantly as a result of electron ‘leak’ during mitochondrial oxidative phosphorylation.
Mitochondrial dysfunction that occurs with ageing results in increased production of ROS

Question 25

what are the bodys defence system to free radicals

Answer 25

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

Question 26

How do the antioxidant works

Answer 26

they have a large number of electron in the shell, they donate an electron to the oxygen free radical and stablise the free radical

Question 27

what do we use free radical for

Answer 27

immunological response system.

Question 28

how are free radicals used in the immunological response system

Answer 28

- Macrophages engulf bacteria | - Free radical reactions produced inside the macrophage oxidize and kill bacteria

Question 29

what is autophagy

Answer 29

– this is a intraceullar degradation system that delivers cytoplasmic constituents to the lysosome

Question 30

what is used to degrade and get rid of the unfolded protein

Answer 30

- Autophagy and proteasomal degradation get rid of the unfolded protein

Question 31

how can an unfolded protein get refolded

Answer 31

chaperones

Question 32

what does aggregation lead to

Answer 32

leads to ageing | proteins

Question 33

what does cross linked proteins result in

Answer 33

- The accumulation of cross-linked proteins damage cells and tissue slowing down bodily processes

Question 34

give an example of a disease that can be caused by cross linking proteins

Answer 34

Alzheimers disease - Aggregation and cross linking of the beta amyloid protein - Also get crossing linking which makes it harder to get rid of Another example - Non-enzymatic glycosylation reactions occur when glucose molecules attach to proteins causing a chain of chemical reactions resulting in a structural change to the proteins.

Question 35

what are the consequences of cross linking proteins

Answer 35

- Loss of flexibility of connective tissue | - Microvascular changes in arteries

Question 36

what is genomic instability

Answer 36

- Refers to a high frequency of mutations within the genome

Question 37

when does a somatic mutation result from

Answer 37

* Ageing results from an imbalance between the rate of DNA repair and accumulation of DNA damage. * When the damage exceeds repair, the cell malfunctions

Question 38

what are the factors of ageing

Answer 38

- Mulfacturial - Progressive - Deleterious

Question 39

what is nutrient sensing

Answer 39

* Nutrient sensing is a cell's ability to recognize and respond to fuel substrates such as glucose. * Homeostatic mechanisms respond to different hormones (e.g. insulin; IGF-1) to maintain blood glucose at physiological levels

Question 40

what happens to nutrient sensing during ageing

Answer 40

* In old age, these mechanisms become disrupted and result in consequences which underpin disease including: * Reduced insulin sensitivity resulting in glucose intolerance * Increase in visceral fat mass

Question 41

what postpones senescene

Answer 41

Caloric restriction postpones senescence - Food restricted rats show less evidence of cancer, atherosclerosis, and autoimmune disease.

Question 42

name some process fo epigenetic alternations

Answer 42

``` DNA methylation Chromatin structure Histone modification Regulatory RNA Spatial organisation of chromosomes ```

Question 43

what does stem cell exhaustion of ... lead to - HSCs - MSCs - satellite cells - IESCs

Answer 43

- anaemia and myelodysplasia - oeteoporosis and decreased fracture repair - decreased repair of muscle fibres - decreased intestinal function

Question 44

what are the ways that we can reverse ageing

Answer 44

– loose stem cells, eliminate damaged cells, epigenetic drugs – can reverse some of the changes, activate chaperones to reactivate the proteins, telomerase reactivation, elimination of damaged cells

Question 45

what happens to hearts as we age

Answer 45

- 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.