The cellular aspects of ageing Flashcards
what is ageing
- Gradual and spontaneous changes occur in maturation from infant to adulthood, these changes underpin a normal physiological decline seen in middle and late adulthood
ageing is a
- Ageing is a biological process not a disease
what are the consequences of ageing
- Reduce tissue and physiological function
- Decreased resistance to stress – physical and psychological
- Increased susceptibility to disease
what are the two broad categories of ageing
cancer and degenerative disease
what are the degenerative diseases of ageing
Alzheimer’s, kidneys disease, heart disease, autoimmune disease, cogntivie decline
what levels does ageing occur at
- Molecules
- Cell
- Tissues
- Organs
how do cells respond to damage or stress
Cells respond to damage or stress via cell death (apoptosis) and arrested cell growth (cell senescence)
what are factors that influence life expectancy
- Disease Processes
- Medical Treatment
- Lifestyle Choices
- Nutrition
- Heredity
what is tumour suppression genes
- these are genes that have evolved to protect from cancer, they can cause the damage cells to die or arrest growth
How do you use genes to study ageing
- Classic genetic approach
- Isolate and study mutants with altered ageing
what are the hallmarks of ageing
- Telomere attrition
- Cellular senescene
- Mitochondrial dysfunction
- Deregulated nutrient sensing
- Loss of proteostatsis
- Epigenic alterations
- Genomic instability
- Stem cell exhaustion
- Altered intracellular communication
what does ageing result from
- Cell intrinsic factors
- Cell extrinsic factors
what does the hay flick limit prove
cell senscene theory
describe how the hay flick limit works
- 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
describe the action of telomerase in normal DNA replication
- 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
describe the telomeric theory of senescene
- 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
where are shortened telomeres found
– Atherosclerosis
– Heart disease
– Hepatitis
– Cirrhosis
describe how telomeric theory link to cancer
• 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
how does alternated intracellular communication lead to ageing
- 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
How does the immune system decline lead to ageing
- 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
what is a free radical
• A free radical is a molecule with an unpaired, highly reactive electron
what does a free radical do to cells and organs
• During aging, damage produced by free radicals causes cells and organs to stop functioning.
name a type of free radical
• 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.
how do mitochondria cause free radical damage
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
what are the bodys defence system to free radicals
– 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.
How do the antioxidant works
they have a large number of electron in the shell, they donate an electron to the oxygen free radical and stablise the free radical
what do we use free radical for
immunological response system.
how are free radicals used in the immunological response system
- Macrophages engulf bacteria
- Free radical reactions produced inside the macrophage oxidize and kill bacteria
what is autophagy
– this is a intraceullar degradation system that delivers cytoplasmic constituents to the lysosome
what is used to degrade and get rid of the unfolded protein
- Autophagy and proteasomal degradation get rid of the unfolded protein
how can an unfolded protein get refolded
chaperones
what does aggregation lead to
leads to ageing
proteins
what does cross linked proteins result in
- The accumulation of cross-linked proteins damage cells and tissue slowing down bodily processes
give an example of a disease that can be caused by cross linking proteins
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.
what are the consequences of cross linking proteins
- Loss of flexibility of connective tissue
- Microvascular changes in arteries
what is genomic instability
- Refers to a high frequency of mutations within the genome
when does a somatic mutation result from
- Ageing results from an imbalance between the rate of DNA repair and accumulation of DNA damage.
- When the damage exceeds repair, the cell malfunctions
what are the factors of ageing
- Mulfacturial
- Progressive
- Deleterious
what is nutrient sensing
- 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
what happens to nutrient sensing during ageing
- 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
what postpones senescene
Caloric restriction postpones senescence
- Food restricted rats show less evidence of cancer, atherosclerosis,
and autoimmune disease.
name some process fo epigenetic alternations
DNA methylation Chromatin structure Histone modification Regulatory RNA Spatial organisation of chromosomes
what does stem cell exhaustion of … lead to
- HSCs
- MSCs
- satellite cells
- IESCs
- anaemia and myelodysplasia
- oeteoporosis and decreased fracture repair
- decreased repair of muscle fibres
- decreased intestinal function
what are the ways that we can reverse ageing
– 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
what happens to hearts as we age
- 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.
