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.
