theories of aging chapter 2. outline 1.mechanisms of aging 2.general theories of aging a. aging by...

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  • Theories of Aging

    Chapter 2

  • OutlineMechanisms of Aging

    General theories of aginga. Aging by Programb. Gene Theoryc. Gene Mutation Theoryd. Cross-Linkage Theorye. Free Radical Theoryf. Cellular Garbage Theoryg. Accumulation-of-Errors Theoryh. Wear-and-Tear Theoryi. Auto-Immune TheoryNew AntigensIncrease in Auto-Immune Reactions

  • Aging is characterized by a general reduction in functional capabilities and by structural changes in the body.

    Q: What causes the changes associates with aging?

    If the underlying cause of aging can be determined, it might be possible to interfere with the process, thus, extending human longevity

    Goal of increasing human life span can be attained either bysuppressing the cause of death in younger peopledelaying the aging process that make us more susceptible to disease and death as we grow older

  • Mechanisms of AgingBiological components of humansThey contain cell that continue to divide and produce as long as the person is alive (the rate of cell division decreases w/ age)

    Post-mitotic cells: type of body cells that actively dividing during embryonic development, but incapable of dividing after birth (no longer capable of undergoing mitosis; e.g, nerve and muscle cells)

    Intercellular substance: large components of non-cellular material located b/w cells, such as collagen that provides support in the skin, bone, cartilage, tendons & other tissues

    All 3 subject to physiological controls that function w/in the body

    Early hypotheses:Vigor declines as a result of change in cells that are capable of dividingVigor declines due to loss/injury of cells no longer dividing (nerve & muscle)Vigor declines w/ age due to changes in intercellular materials

  • General Theories of AgingCriteria to validate a proposed theory of aging:Changes must occur commonly in all members of a given species

    The proposed process must be progressive with time (changes must be obvious as the person grows older)

    The process must produce changes that cause organ dysfunctions and ultimately cause a particular body organ or system failure

    Characteristics of the TheoriesLink aging with death of increasing numbers of cells as they wear out for extended usage & prolonged exposure to various deleterious factors

    Mechanical or chemical explanations for cellular changes & dysfunctions that are characteristics of aging

    Self-poisoning that occurs at the cellular level increases steadily w/ age, ultimately reaching levels that cause organism to malfunction or cease to function

    Genetic mechanisms; changes due to somatic mutations or loss of biological info.

  • General Categories of Aging Theories:

    Aging results from some form of damage. An organ or a system becomes worn or damaged, adding more stress on other organs. Damage or excessive wear in one particular organ/system causes a down-ward spiral in body functioning.

    There are non-reversible physical or chemical changes within cells that gradually alter the cellular function

    Aging is genetically programmed by some sort of neurological center that functions as a biological clock ; intrinsic aging chronometer (brain)

  • A. Aging by ProgramBegins at birth, each species has its own average longevity aging is programmed in each species

    The site of localized aging chronometer (time keeper) is Hypothalamus (in the base of the brain)

    Hypothalamus contains centers that control the production of growth hormones by pituitary gland, as well as the development and activities of the gonads (thyroid, adrenal)

    Hormones and neurons carry out the information originated from this center; ability of the organism to transmit the message declines w/ ageDecrease nerve conduction ratesChange in structure & amounts of hormoneReceptors for nerve impulses or hormones may become less capable of reacting appropriately to incoming impulse or molecular message

  • Thymus, lymphoid gland, may be involved in some manner in the programmed regulation of aging.

    It atrophies at the onset of adolescence, implying that aging occurs more readily in the absence of thymus

    Some research exclude the role of central nervous system in programmed aging

    Each normal cell type has a finite number of divisions and then die.(fibroblasts taken from embryo divide 50 times, if take from adult only divide 20X)

    Cells isolated from patients suffering from Werners syndrome only divide 10-20 times

    Werner syndrome: rare condition in which affected individuals show advanced signs of aging while still in their twenties

    These suggest that cell death is an inherent property of the cells, rather than being controlled by hypothalamus or some other aging chronometer

  • Explanation for programmed longevity:Perhaps only in early life do the genes produce mRNA, tRNA, rRNA, and enzymes. As cells grow old these substances will be used up & if not replenished, cells will cease functioning

    The amount of these substances in each cell can specifically limit the number of divisions of that particular cell type

    Q: how can there be life long division of many cell types in the body if each cell type is capable of only a limited number of cell divisions?

    There are several generations of dormant renewal cells in each tissue that begin dividing at different These are, in effect, reserve embryonic cells. Only when these are used will the tissue begin to show signs of aging.

  • General consensus about aging by program: Its unlikely that aging results from the loss of capacity to divide, rather the finite division capacity of cells shown in culture is rarely, if ever, reached in the body. Thus, the reactions of at least some cells in the body is different than when they are cultured.

    Cells that are under constant stress (such as cells lining the intestine, those in active layer of epidermis, RBCs) undergo more than 50 division during a persons life.

    Other functional losses that occur in cells produce physiological dysfunctions in the cells. This causes the cells to show aging changes before they reach their finite limits to divide.

  • B. Gene TheoryThe gene theory suggests that: Aging is programmed but due to one or more harmful genes within each organism

    These harmful genes become active only late in life and alter the physiology of the organism in ways that result in its death

    Alternatively, there are genes that direct cellular functions in early years and become altered in later years, thus, altering their function

    In their altered state, these genes may be responsible for the functional decline and structural changes associated with aging

    Gene theory suggests: Human life span is an inherited trait (support: studies of twins)

    There is considerable similarity in age at death of pairs of monozygous (single egg) twins, whereas this is not apparent in dizygous (2 eggs) twins

  • C. Gene Mutation TheoryMutations occur in the genes of cells composing the various tissues during life which alter the functioning of the cells, generally to the detriment of the cells

    Gene mutation theory: Accumulation of cells w/ altered structure and function that results from these mutations may lead, w/ the passage of time, to malfunctions and eventually death

    Natural Radiation accelerates aging process (mouse liver cells)

    Gene composition: Nucleotide; NT (sugar, base, phosphate molecule), NTs joined together to form double stranded DNA (deoxyribonucleic acid)

    Damaged DNA can be repaired accomplished by enzymes w/in the cell cutting out the damaged region of the gene & adding back a new set of NTs, utilizing the undamaged strand as template

    With the passage of time, gene repair mechanisms become less efficient, some mutations remain uncorrected, thus, causing structural and functional aging changes (damaged DNA, mRNA, ribosomes)

  • D. Cross-linkage TheoryProteins (building blocks of cells) are composed of peptides. Protein denaturation is irreversible (e.g., cooked egg is denatured and its physical state is changed permanently. Protein denaturation is caused by the formation of cross-links between peptide strands, which causes structural and functional changes in protein.Cross-linkers are chemicals that develop between hydrogen atoms in the peptide

    Cross-linkage theory: With age & formation of new cross-links, the structure of some proteins in the cells is irreversibly altered. protein function alters organ/ system dysfunction (e.g., enzymes and collagen)

    Enzymes: organic catalysts; accelerate the rate of chemical reactions (digestions, metabolism, etc.)

    Collagen: metabolically inert supportive tissue located between cells, composed of protein fibers embedded in intercellular matrix.Collagen structural changes is responsible for loss of blood vessel elasticity that occurs with age

  • Increase in collagen deposition w/ aging excess fibers: Fibrosis

    Collagen is important component of connective tissue (CT). When specific cells/ tissues die, replaced by CT which lacks functional capabilities of original cellsAlso interfere with oxygen and nutrient supplyExample: Elastic fibers in skin degenerate with age replaced by collagen fibers that are less flexible elasticity of skin decreases with age

    Molecular changes in the matrix surrounding collagen fibers also occur w/ age less permeable capillaries less permeable reduced transport of gas, nutrients, waste across their walls significantly affects metabolism (e.g., kidney: decreased filtration, renal failure

    The theory also suggests: some essential molecules, other than pr., may become cross-linked w/age (example: DNA

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