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Reference: Developmental biology - Scott F.Gilbert

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  2. 2. Gerontology (from Greek:  geron, "old man" and-logy,  "study of") is the study of the social, psychological  and biological aspect of aging.   It is distinguished fromgeriatrics, which is the branch  of medicine that studies the diseases of the elderly. Characteristics of aging affect all the individuals of a species. Two major topics in research on aging 1) Life span 2) Senescence These topics are interrelated.
  3. 3. Many evolutionary biologists consider senescence to be the default state occuring after the animal has fulfilled the requirements of natural selection. After its offspring are born and raised,the animal can salmon Recent studies indicate that there are genetic components that regulate rate of aging.Altering activity of these genes can alter lifespan of an individual.
  4. 4. The maximum lifespan is a characteristic of a species; It is the maximum number of years a member of species has been known to survive. Life expectancy is not a characteristic of species,but of populations It is the age at which half the population still survives.
  5. 5. Life expectancy of Indians  ♂ ♂      -     65.77 years     ;      ♀ ♀      -  67.95 years
  6. 6. Nuclear pyknosis: With advancing age, the nucleus shrinks and stains deeply. This is due to the condensation of the nuclear material. Aging is accelerated by chromosomal aberrations,and somatic gene mutations Degeneration of cytoplasmic organelles
  7. 7. Changes in enzymatic proteins LDH,SDH,AC Pase,Lysosomal enzymes Catalase,Glutathione peroxidase Respiratory enzymes,Alkaline phosphatase,Glucose dehydrogenase
  8. 8. Shortening of telomeres telomeres -specific DNA sequences found only at the tips of chromosome. protect the tips of chromosomes from erosion and from sticking to one another. in most normal body cells each cycle of cell division shortens the telomeres. Eventually, after many cycles of cell division, the telomeres can be completely gone and even some of the functional chromosomal material may be lost. erosion of DNA from the tips of our chromosomes contributes greatly to aging and death of cells.
  9. 9. Accumulation of aging pigments Lipofuscin accumulation
  10. 10. Accumulation Accumulation of free radicals of free radicals Free radicals produce oxidative damage in lipids, proteins, or nucleic acids by “stealing” an electron to accompany their unpaired electrons. Some effects are wrinkled skin, stiff joints,and hardened arteries. Normal metabolism—for example, aerobic cellular respiration in mitochondria—produces some free radicals. Others are present in air pollution, radiation, and certain foods we eat. Naturally occurring enzymes in peroxisomes and in the cytosol normally dispose of free radicals.
  11. 11. Changes in hormonal levels Ward Dean M.D.
  12. 12. Weakened immune system With age the system's ability to produce necessary antibodies that fight disease declines the immune system may start to attack the body’s own cells. This autoimmune response might be caused by changes in cell-identity markers at the surface of cells that cause antibodies to attach to and mark the cell for destruction.
  13. 13. Decrease in rate of celldivision The Hayflick Limit Theory of Aging says that the human cells ability to divide is limited to approximately 50-times, after which they simply stop dividing (and hence die). Leonard Hayflick
  14. 14. Glucose, the most abundant sugar in the body, plays a role in the aging process. It is haphazardly added to proteins inside and outside cells, forming irreversible cross-links between adjacent protein molecules. With advancing age, more cross-links form, which contributes to the stiffening and loss of elasticity that occur in aging tissues.
  15. 15. The changes occuring in the intercellular spaces and in the lumen of blood vascular system are examples of extracellular changes. Dementia Dementia (taken from Latin, originally meaning "madness", from de"without" + ment, the root of mens "mind") is a serious loss of cognitive ability . dementia is common in the geriatric population, Dementia is a non-specific illness syndrome (i.e., set of symptoms) in which affected areas of cognition may be memory, attention, language, and problem solving. one of the most common forms of dementia is Alzheimer's disease
  16. 16. Alzheimer’s disease In Alzheimer’s disease, a substance called amyloid builds up and causes the early death of brain cells, which results in a progressive loss of memory and other brain functions.
  17. 17. Atherosclerosis Atherosclerosis is a disease in which plaque builds up inside arteries. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. Over time, plaque hardens and narrows arteries. This limits the flow of oxygen-rich blood to organs and other parts of body. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death.
  18. 18. Fibrosis Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue . This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue. Eg: cirrhosis of the liver. cirrhosis of the liver fibrosis in heart
  19. 19. Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system. The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the region of the midbrain; the cause of this cell death is unknown., the most obvious symptoms are movement-related; these include shaking, rigidity, slowness of movement and difficulty with walking and gait. dementia commonly occur in the advanced stages of the disease. Other symptoms include sensory, sleep and emotional problems. PD is more common in the elderly-after the age of 50.
  20. 20. Changes in collagen There is an increase in the amount of collagen proteins deposition in the intercellular spaces. This influences the permeability of cell membranes, affects the speed of diffusion of substances in and out and significantly influences the process of aging.
  21. 21. Aging and Wrinkles Wrinkles are a by-product of the aging process. With age, skin cells divide more slowly, and the inner layer, called the dermis, begins to thin. The network of elastin (the protein which causes skin to stretch) and collagen fibers (the major structural proteins in the skin), which support the outer layer, loosen and unravel, causing depressions on the surface. With aging, skin also loses its elasticity, is less able to retain moisture, oil-secreting glands are less efficient and the skin is slower to heal. All of these contribute to the development of wrinkles
  22. 22. Oxidative damage Aging is a by-product of normal metabolism; About 2- 3% of the oxygen atoms taken up by the mitochondria are reduced to reactive oxygen species (ROS). [Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen ] These ROS include the superoxide ion, the hydroxyl radical, and hydrogen peroxide. ROS can oxidize and damage cell membranes, proteins, and nucleic acids. Evidence for this theory includes the observation that Drosophila that overexpress enzymes that destroy ROS (catalase and superoxide dismutase) live 30 -40% longer than do controls .
  23. 23. Moreover, flies with mutations in the methuselah gene live 35% longer than wild-type flies. The methusaleh mutants have enhanced resistance to paraquat, a poison that works by generating ROS within cells . These findings not only suggest that aging is under genetic control, but also provide evidence for the role of ROS in the aging process. In C. elegans, too, individuals with mutations that increase the synthesis of ROS-degrading enzymes live much longer than wild-type nematodes . The evidence for ROS involvement in mammalian aging is not as clear.
  24. 24. Mitochondrial genome damage. It is thought that mutations in mitochondria could (1) lead to defects in energy production, (2) lead to the production of ROS by faulty electron transport, (3) induce apoptosis. A recent report shows that there are "hot spots" for age-related mutations in the mitochondrial genome, and that mitochondria with these mutations have a higher replication frequency than wild-type mitochondria. Thus, the mutants are able to outcompete the wild-type mitochondria and eventually dominate the cell and its progeny. Moreover, the mutations may not only allow more ROS to be made, but may make the mitochondrial DNA more susceptible to ROS-mediated damage.
  25. 25. General wear-and-tear and genetic instability "Wear-and-tear" theories of aging are among the oldest hypotheses .As one gets older, small traumas to the body build up. Point mutations increase in number, and the efficiencies of the enzymes encoded by our genes decrease. if a mutation occured in a part of the protein synthetic apparatus, the cell would make a large percentage of faulty proteins . If mutations arose in the DNA-synthesizing enzymes, the rate of mutations would be expected to increase markedly, . Likewise, DNA repair may be important in preventing senescence, and species whose members' cells have more efficient DNA repair enzymes live longer genetic defects in DNA repair enzymes can produce premature aging syndromes in humans
  26. 26. Progeria [Hutchinson-Gilford syndrome ] Progeria is a disease characterized by normal development in the first year of life followed by rapid aging. It is caused by a genetic defect in which telomeres are considerably shorter than normal. Symptoms include dry and wrinkled skin, total baldness, and birdlike facial features. Death usually occurs around age 13.
  27. 27. Werner syndrome Werner syndrome is a rare, inherited disease that causes a rapid acceleration of aging, usually while the person is only in his or her twenties. It is characterized by wrinkling of the skin, graying of the hair and baldness, cataracts, muscular atrophy, and a tendency to develop diabetes mellitus, cancer, and cardiovascular disease. Most afflicted individuals die before age 50.
  28. 28. In C. elegans, there appear to be at least two genetic pathways that affect aging. The first pathway involves the decision to remain a larva or to continue growth. After hatching, the C. elegans larva proceeds through four instar stages, after which it can become an adult or (if the nematodes are overcrowded or if there is insufficient food) can enter a nonfeeding, metabolically dormant dauer stage. It can remain a dauer larva for up to 6 months, rather than becoming an adult that lives only a few weeks.
  29. 29. In the dauer stage, adult development is suppressed, and extra defenses against ROS are synthesized. If some of the genes involved in this pathway are mutated, adult development is allowed, but the ROS defenses are still made. The resulting adults live twice to four times as long as wild-type adults The pathway that regulates dauer formation & longevity – insulin signalling pathway
  30. 30. Insulin like protein + DAF2 TGF –β Mediated signal DAF9 Steroid hormone DAF12 Dauer larva Gene response for reproductive growth
  31. 31. Proposed mechanism for extending lifespan of C.elegans through insulin signalling pathway
  32. 32. The second pathway involves the gonads. Germ cells appear to inhibit longevity, when these cells are removed ,C.elegans live longer. Germ line stem cells produce a substance that blocks the effects of a longevity- inducing steroid hormone
  33. 33. The insulin signalling pathway also regulates lifespan in Drosophila. Flies with weak loss-of-function mutations of insulin receptor gene live nearly 85% longer than wild type. The insulin signalling pathway also regulates lifespan in mammals. 1] mice with loss-of-function mutations of insulin signalling pathway live longer than wild type. 2]dog breeds with low levels of insulin-like growth factor[IGF1] live longer than those breeds with higherlevels of this factor. 3]mice lacking 1 copy of IGF1 receptor gene live 25% longer than wild type.
  34. 34. As human life expectancy increases due to our increased ability to prevent and cure disease, we are still left with a general aging syndrome that is characteristic of our species. However our knowledge of regeneration is being put to use by medicine,and we may soon be able to ameliorate some of the symptoms of aging