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Effects of Air Pollution on the Health of Older Adults

Effects of Air Pollution on the Health of Older Adults. What is the Nature of Aging? Nancy L. Nadon, Ph.D. Biology of Aging Program National Institute on Aging. What is the Nature of Aging?. Overview of biology of aging at the tissue, cellular and molecular level

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Effects of Air Pollution on the Health of Older Adults

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  1. Effects of Air Pollution on the Health of Older Adults What is the Nature of Aging? Nancy L. Nadon, Ph.D. Biology of Aging Program National Institute on Aging

  2. What is the Nature of Aging? • Overview of biology of aging at the tissue, cellular and molecular level • Age-related changes in the pulmonary system • Age-related changes in the immune system • Interaction of the age effect with the response to air pollution • Use of animal models to study the effect of air pollution on the aged

  3. Aging - • Loss of cells or cell function leading to a reduction of function at the physiological level • Separate from age-related diseases, although may be related mechanistically • Effects of pollution exposure are likely impacted by both normal aging changes and age-related diseases

  4. Aging - • Cell death • Reduction in ability of stem cells or progenitor cells to divide and differentiate • Reduction in repair of cellular components • Accumulation of oxidative damage • Genomic instability and changes in gene expression

  5. Stressors: Inflammation, Oxidative stress, Nutrition, Environmental exposures Cell loss, damage or dysfunction Age-related loss of function – frailty, susceptibility to disease, etc.

  6. Young Repair Damage Loss Aged Repair Damage Loss Damage / Repair Balance Changes with Age

  7. Example - Sarcopenia Molecular changes in satellite cells with decrease in signaling capacity Reduction in proliferation and differentiation needed to injured muscle cells Loss of muscle Frailty

  8. Age-related changes in Respiratory Function Static Elastic Recoil Chest wall compliance Respiratory muscle strength Gas exchange surface area Response to hypoxia Lung volume Maximum inspiratory and expiratory pressure

  9. Aging Disease Pulmonary Function Environmental Exposures Other Exposures

  10. Studies in animal models allow control of some of the factors that influence pulmonary function: • Environment – air quality • Diet • Health status • Genetic background

  11. Genetic differences between rodent strains can be used to model specific aspects of human aging, disease, and response to stressors. No one model is optimal for all aspects of aging. Awareness of the differences between strains and substrains is important when using rodent models.

  12. Sprague Dawley rats and F344 rats have a significant difference in thoracic gas volume, even when corrected for body weight. SD F344 Specific thoracic 22.2 19.1 gas volume (ml/Kg) Significant at p< 0.05 From Boyd et al., 1982

  13. SD rats had an age-associated increase (69%) in air spaces while F344 rats did not have a significant change. From Kerr et al., 1990, Exp. Gerontol. 25:563-574. One study demonstrated an increase in lung volume in F344 with age, but this increase correlated with an increase in body weight. From Pinkerton et al., 1982, Am. J. Anat. 164:155-74

  14. Age-related changes in innervation may play a role in the decreased response to stress in aged. • Innervation of the smooth muscle of the trachea and the bronchial tree is reduced in aged rats. • Innervation of pulmonary artery is decreased in aged rats. From Ricci et al., 1997, Mech. Ageing Dev. 99:245-255.

  15. NO production decreases with age in the aorta but not in the pulmonary artery. From Tschudi et al., 1996, J. Clin. Invest. 98:899-905.

  16. Immune system function also decreases with age • Elderly have higher rates of respiratory infections, do not mount as robust a response to infection as do the young. • Changes in innate immunity with age also impact response to pollution. • Age-related changes in the pulmonary system decrease effectiveness of the cough, reduce the ability to clear mucous, increasing susceptibility to infection.

  17. Macrophage function declines with age: • iNOS expression decreases • Synthesis of NO intermediates decreases • ROS production decreases • Expression of IL-6 and TNFα decrease • PGE2 production increases • Contributes to reduced dendritic cell function • Contributes to impaired T cell response From Plackett et al., 2004, J. Leukocyte Biol. 76:291-299

  18. Other age-associated changes in innate immunity • Neutrophils – defects in intracellular signaling that reduce microbiocidal function • Dendritic cells – reduced ability to stimulate B and T cells • NK cells – decreased tumoricidal activity

  19. Interactions between age effects and effects of exposure to pollution Some effects of age and exposure to pollution are similar and may have common mechanisms. Caloric restriction: • Moderates and/or delays onset of age-associated phenotypes • Protects against ozone-induced damage to lungs* * From Elsayed, 2001, Toxicol. 159:171-182.

  20. Response to pollution is specific for type of pollutant • Fine particle pollution – almost 10-fold increase in incidience of arrythmias • Gaseous pllution – no significant increase in arrythmias From Nadziejko et al., 2004, Inhal. Tox. 16:373-380.

  21. With ozone-induced injury models, there is evidence of an age effect on level of injury • 24 month old F344 rats had a higher level of injury to alveolar ducts and epithelium than 9 mo. old. • Repair of damage, as measured by cell division to replace damaged cells, was as good in the old as in the young rats. From Vincent and Adamson, 1995, Am. J. Pathol. 146:1008-1016.

  22. Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterial toxin.Elder AC, Gelein R, Finkelstein JN, Cox C, Oberdorster G.Inhal Toxicol. 2000;12 Suppl 4:227-46.

  23. Age alone influenced the response to fine particle pollution • Aged rats showed: • 30% decrease in neutrophils from bronchoalveolar lavage • 86% increase in resting respiratory burst • 129% increase in PMA-stimulated respiratory burst From Elder et al., 2000, Inhal Toxicol. 12 Suppl 4:227-46.

  24. Age influenced the effect of ozone exposure, endotoxin exposure and fine particle exposure Treatment Effect on unstimulated Respiratory Burst No treatment aged ≈ young Fine particle (FP) aged < young Ozone aged > young FP + O3 aged > young LPS aged ≈ young LPS + FP aged ≈ young LPS + O3 aged >> young LPS + FP + O3 aged >>>> young From Elder et al., 2000, Inhal Toxicol. 12 Suppl 4:227-46.

  25. Working with rodent models • Advantages: Control diet, environment, health, genetics • Many considerations: appropriate ages and number of time points, sample sizes, choice of strain

  26. The Development of Emphysema in Cigarette Smoke-exposed Mice Is Strain Dependent Guerassimov et al., Am. J. Resp. Crit. Care Med. 170:974-980, 2004. 5 strains compared: NZWLac/J, C57BL6/J, A/J, SJL/J, AKR/J

  27. 4 of the 5 strains showed significant increases in Lm The same 4 of 5 strains showed significant increases in inflammatory cells and cytokines 1 of the 5 strains (NZW) did not have a significant change in Lm NZW also did not have a significant change in inflammatory cells or cytokines From Guerassimov et al.,Am. J. Resp. Crit. Care Med. 170:974-980, 2004

  28. Phenotypic variation in cardiovascular responses to acute hypoxic and hypercapnic exposure in mice Campen et al., 2004, Physiol. Genomics 20: 15-20. A/J, BALBc/J, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, FVB/J DBA/2J showed a different response than the other 6 strains, huge increase in frequency of arrythmias

  29. Strain differences in lung mechanics C3H/HeJ A/J C57BL/6J B6C3F1 Functional 0.37* 0.27 0.25 0.28 Residual Capacity(ml) Total Lung 1.44* 1.01 0.95 0.89 Capacity(ml) Lung 0.126*0.079 0.057 0.053 Compliance (ml/cm H2O) * Significant at p<0.01 From Tankersley et al., 1999, Am. J. Physiol. 99:764-769.

  30. From Schulz, MPD 16, Mouse Phenome Database, The Jackson Laboratory, http://www.jax.org/phenome, analyzed 3/19/05.

  31. From Schulz, MPD 16, Mouse Phenome Database, The Jackson Laboratory, http://www.jax.org/phenome, analyzed 3/19/05.

  32. From Kitten et al., MPD 151, Mouse Phenome Database, The Jackson Laboratory, http://www.jax.org/phenome, analyzed 3/19/05.

  33. Many factors to consider in use of rodents to model age-related changes in response to exposure to pollution • Strain and gender • Ages and time-points • Husbandry and housing

  34. NIA Resources • NIA resources pagehttp://www.nia.nih.gov/ResearchInformation/ScientificResources/ • Aged rodent colonies information handbook • Aged rodent tissue bank • Aged rodent tissue arrays • rodents@nia.nih.gov

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