cellular aspects of ageing Flashcards
what are the consequences of ageing?
- Reduced tissue/physiological function
- Decreases resistance to stress (both physical and psychological)
- Increases susceptibility to disease (age-related diseases)
what are the 2 broad categories of ageing?
cancer
degenerative disease
what levels does ageing occur at?
molecules
cells
tissues
organ systems
what is cellular ageing a response to?
damage or stress
what do tumour suppressor genes do?
cause damaged cells to die or arrest growth (undergo apoptosis or senescence)
what are responses to cellular ageing?
cell death (apoptosis) or cell senescence (arrested cell growth)
what factors affect life expectancy?
- Disease processes
- Medical treatment
- Lifestyle choices
- Nutrition
- Heredity
what are the hallmarks of ageing?
altered intercellular communication genomic instability stem cell exhaustion cellular senescence mitochondrial dysfunction deregulated nutrient-sensing loss of proteostasis epigenetic alteration telomere attrition
what is the programmed senescence theory?
- 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
what is the telomeric theory of senescence?
- 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
what are telomeres?
- Telomeres are specialized DNA sequences at the end of chromosomes.
- Non coding repeats of sequence TTA GGG
what does telomerase do?
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
what conditions are shortened telomeres found in?
Atherosclerosis, heart disease, hepatitis, cirrhosis
what is a free radical?
molecule with unpaired, highly reactive electron
how are oxygen free radicals produced?
produced during metabolism or bc of environmental pollution
how are reactive oxygen species made?
produced predominantly as a result of electron ‘leak’ during mitochondrial oxidative phosphorylation.
what does mitochondrial ageing result in?
increased production of ROS
what is the body’s defence system against free radicals?
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.
how do antioxidants deal with free radicals?
Antioxidant has so many electrons in its outer shell that it doesn’t matter too much if it loses one
what is autophagy?
an intracellular degradation system that delivers cytoplasmic constituents to the lysosome
what does an accumulation of cross linked proteins do?
damages cells and tissue
in what conditions are an accumulation of cross linked proteins found?
Alzheimer’s disease
Non-enzymatic glycosylation
what happens in Non-enzymatic glycosylation?
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 non-enzymatic glycosylation reactions?
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.
how does DNA lead to ageing?
an imbalance between rate of DNA repair and accumulation of DNA damage leads to ageing
what is nutrient sensing?
a cell’s ability to recognize and respond to fuel substrates like glucose.
how does downregulated nutrient sensing occur and how does this lead to disease?
homeostatic mechanisms become disrupted
leads to Reduced insulin sensitivity resulting in glucose intolerance
Increase in visceral fat mass
what effect does caloric restriction have on ageing?
prolongs life and improves quality of life
what is epigenetics?
factors affecting DNA expression that arent changes in DNA
why is there an exhaustion of the stem cell pool?
depletion due to loss of self-renewal and due to senescence
what changes in heart function occur during ageing?
- 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.
