16 - Cellular ageing

Question 1

What is cellular ageing?

Answer 1

gradual and spontaneous changes that occur in maturation from infant to young adult

Question 2

What are the consequences of ageing?

Answer 2

• Reduced tissue/physiological function
• Decreases resistance to stress – physical and psychological
• Increased susceptibility to disease

Question 3

What are the factors influencing life expectancy?

Answer 3

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

Question 4

What are the 3 stages of cellular ageing?

Answer 4

o Repair
o Senescence – arrested cell growth
o Death – apoptosis

Question 5

What is programmed senescence theory?

Answer 5

 Cells grown and removed and repeated
 Eventually cells stopped growing – described as the Hayflick limit
 Theory = telomeric theory
 Non-coding repeats of TTA GGG that deplete with each division
 When they become too short, the cell enters senescence
 Telomerase fills the gap by attaching bases to fill in the gaps
 Keeps the telomeres long enough but its function and levels decline with age and the telomeres become shorter and shorter

Question 6

What is endocrine theory?

Answer 6

 Biological clocks act through hormone sot control the pace of ageing
 Hormones affect growth, metabolism, temperature, inflammation and stress
 E.g. menopause

Question 7

What is immunologic theory?

Answer 7

 Programmed decline in immune system leads to an increased vulnervaility to disease, ageing and death
 E.g. involution of the thymus gland

Question 8

How does caloric restriction prolong life?

Answer 8

• Induces levels of antioxidant enzyems and downregulates IGF-1

Question 9

What are the hallmarks of ageing?

Answer 9

• Epigenetic alterations
o DNA methylation
o Histone modifications
o Regulatory RNAs
o Chromatin structure
• Set cell exhaustion
o Stem cells responsible for normal maintenance and repair
o Stem cell function loss due to surrounding damaged cells or damage to the cells themselves
o Loss of stem cells mean maintenance and repair cannot take place as well

Question 10

What are the programmed theories?

Answer 10

Ageing has a biological timetable to internal clock
Programmed senescence theory
Endocrine theory
Immunologic theory

Question 11

What are the error theories?

Answer 11

Ageing is a result of internal or external assaults that damage cells or organs so that they can no longer function properly
Mitochondrial free radical theory 
Wear and tear theory
Cross-linking theory 
Catastrophe theory 
Somatic mutation theory 
Dysregulated nutrient theory

Question 12

What is mitochondrial free radical theory?

Answer 12

 Free radical = molecule with an unpaired, highly reactive electron
 ROS (oxygen free radical) produced as a normal by-product of oxidative phosphorylation in mitochondria
 Increased with age and causes more damage to mitochondria to cause more ROS production
 Defences against free radicals include natural and dietary antioxidants and enzymes uch as superoxide dismutase and catalase

Question 13

What is the wear and tear theory?

Answer 13

 Years of damage to cells, tissues and organs eventually wears them out, killing them and the body

Question 14

What is the cross-linking theory?

Answer 14

 Accumulation of cross-linked proteins damages cells and tissues, slowing down bodily processes
 Loos of flexibility within connective tissue
 Microvascular changes in arteries

Question 15

What is catastrophe theory?

Answer 15

 Damage to system that synthesise or modify proteins in the body
 Faulty proteins accumulate and can damage cells, tissue and organs
 E.g. Alzheimer’s disease
 Fate of unfolded protein
• Refolded by chaperone
• Degraded by autophagy
• Degraded by proteasome by ubiquitin pathways
• Ageing

Question 16

What is the somatic mutation theory?

Answer 16

 Ageing is an imbalance between rate of DNA repair and accumulation of DNA damage
 When the damage exceeds repair, cell malfunctions

Question 17

What is the dysregulated nutrient sensing?

Answer 17

 Mechanisms controlling body fuel levels become disrupted and result in visceral in visceral fat and type 2 diabetes