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Ageing & Muscle (Theories of ageing (Programmed ageing Belief that…

- - - - Oxidative damage
        Strand breaks in DNA/modification of bases
        
        May cause heritable mutations in germ cells
        
        May cause cancer in somatic cells
        
        Oxidation of PUFAs in lipids
        
        Lipid peroxides involved in atherogenesis
        
        Lipid peroxide breaks down to dialdehydes which modify proteins and nucleic acid bases
        
        Oxidation of amino acids in proteins
        
        May lead to formation of antibodies against modified protein
        
        Oxidised amino acids may catalyse further formation of oxygen radicals
      - Free radical defences
        Enzymatic
        
        Superoxide dismutase
        
        Catalase
        
        Glutathione peroxidase
        
        Protein binding of metal ions
        
        Iron bound by transferrin, haemosidierin, ferritin
        
        Copper bound by caeruloplasmin
        
        Metal ions bound by metallothionein
        
        Diet derived antioxidants
        
        a-tocopherol
        
        Ascorbic acid
        
        Polyphenolics (flavanoids, anthocyanins, resveratrol, catechins)
        
        Carotenoids (b-carotene, lycopene, zeaxanthin, capsanthin, lutein
- - - - Structure
        Hundreds of muscle fibres bundles together and contained with layer of connective tissue called endomysium
        Each bundle is known as a fascicle
        Connective tissue surrounding the fascicle is perimysium
        Fascicles bundled together and surrounded by a layer of collagen fibres called epimysium
        Blood vessels run through the endomysium providing oxygen and nutrients to the muscle and remove waste products
        Most muscles attached to the bone by a tendon
        
        Muscle fibres
        
        Can be up to 35cm in length
        
        The cytoplasm is called the sarcoplasm
        
        Sarcoplasm contains more mitochondria and is rich in glycogen and myoglobin compared to cytoplasm of other cells
        
        Muscle fibres surrounded by plasma membrane called the sarcolemma
        
        Myofibrils are protein filaments that run the length of the muscle fibre
        
        Muscle fibres are multinucleate containing hundreds of nuclei inside the sarcoplasm
        
        Myofibrils
        Protein filaments that run the length of the muscle fibre
        Myofibril are surrounded by a tabular network (Sarcoplasmic reticulum)
        
        Regulates storage and release of calcium ions that are required for muscle contraction
        
        Sarcoplasmic reticulum
        The openings across the surface of the sarcolemma extend into the sarcoplasm forming tubules (T-tubules) containing extracellular fluid
        
        The transverse tubules (T-tubules) help conduct electrical impulses into the cell
        
        The sarcoplasmic reticulum is enlarged at the point it meets the T-tubule known as the terminal cisternae
        The T-tubule and the terminal cisternae on each side known as a triad
        
        The conduction of electrical impulses along the T-tubule causes calcium ions within the terminal cisternae to be released, which is the first stage of muscle contraction
      - Contraction
        
        Myofibrils are made up of protein filaments
        Thick filament - myosin
        Thin filament - actin
        The filaments are arranged in sarcomeres, which are the smallest functional unit of a muscle
        
        Thick and thin filaments form bands, which give the striated appearance under a microscope
        
        It is the release of calcium ions within the terminal cisternae that allows the filaments to interact and contract
        
        Myosin (thick)
        
        Made up of two myosin units twisted together
        
        Actin (thin)
        
        Made up of four proteins
        
        Has binding sites for myosin
        
        At rest the binding sites are blocked by strands of tropomyosin
        
        Troponin holds the tropomyosin in position
        
        Key proteins:
        
        Actin
        
        Troponin
        
        Tropomyosin
        
        Stages
        
        Calcium ions released by sarcoplasmic reticulum binds to actin filament, specifically the troponin which causes the tropomyosin to move out of the way of the myosin binding site
        
        The myosin heads can then interact with the actin binding sites forming cross bridges
        
        The myosin head used ATP to pivot, pushing the actin along (power stroke)
        
        ADP and phosphate are released as a by-product of using ATP
        
        The myosin head detaches from the actin binding site when an ATP molecule bind to the myosin
        
        The binding site on the myosin is exposed again, allowing another cross bridge to form
        
        Power strokes continue several times each second, pushing the actin along
        
        This causes the muscle to shorten
        
        Electrical impulse
        When we choose to make voluntary movements, nerve impulses are conducted from the brain, along neurons, to the muscles
        Motor neurons within the somatic (voluntary) nervous system run from the brain or spinal cord to the muscle fibre. Where the motor neurons meet the muscle fibre, the neuron axon branches branches as much as 10,000 times into a neuromuscular junction
        Each muscle fibre is controlled by one neuron, the neuron is located midway along the length of the muscle fibre
        Acetylcholine (ACh) is a neurotransmitter that changes the permeability of a plasma membrane. When an electrical impulse (action potential) reaches the synaptic terminal, vesicles containing ACh fuse with the plasma membrane. ACh is then released into the synaptic cleft.
        ACh diffuses across the synaptic cleft and binds with receptors on the sarcolemma. The permeability of the motor end plate changes causing Na+ to move from the extracellular fluid into the sarcoplasm.
        An action potential is set up due to the increase in Na+, which continues across the sarcolemma and into the T-tubules. Calcium is released and the contraction process starts again.
        The ACh is broken down by acetylcholinesterase
    - - Intercalated disc
        Desmosomes
        
        Intercellular junction
        
        Holds tissue together during strong contraction
        
        Gap Junctions
        
        Ions and small molecules move from one cell to another
        
        Action potential can pass quickly from one cardiac cell to another