2. Comparative and Differential Aging Chapter 3

3. Figure 3.2: Comparison of the relationship of brain weight to life span in vertebrates

4. Figure 3.1: Comparative Maximum Life Spans **Detailed discussion of figure in the legend, pg. 26

5. Drawing of Great Basin Bristlecone Pine (Pinus longaeva). According to dendrochronologists, these trees have been been documented to live up to 5000 years.

7. Figure 3.3: The heterogeneity of the elderly population as illustrated by scores in a hypothetical test.

8. Similar to growth & development life stages, it has been suggested that old age should be divided into consecutive stages: YOUNG OLD: 65-75 years OLD: 75-85 years OLD OLD: 85+ years CENTENARIANS: 100+ years

9. Examples of ways in which the environment may influence the genome 1)Dutch Hunger Winter (World War II): Pregnant mothers gave birth to: - low-weight babies who - when adult showed a greater incidence of diabetes, obesity, coronary heart disease (CHD), cancer - grandchildren of these mothers also inherited the same health problems 2)In some types of mice pregnant mothers were fed folic acid or methyl-rich diets: - pups plus diet had brown fur and good health - pups without diet had increased susceptibility to diabetes

10. Among invertebrates, the most used models have been the fly (Drosophila melanogaster) and the nematode (C. elegans) Suppression of the receptor for insulin/IGF hormone will produce a mutant nematode that will live 6x longer than corresponding controls and be more resistant to all stress. C. Elegans 2 week lifespan hermaphrodite 19,000 genes 959 cells Examples of ways in which environment influences the genome (cont.) 3)

11. In invertebrates, suppression of insulin/IGF-1 receptor and its homologue produces mutants that live longer than controls and resist stress better. Longevity 6X Resistance to stress; Consequences Growth, Development, Metabolism Mechanisms of action Energy metabolism from aerobic to anaerobic Chaperons over-expression Free radical accumulation

12. Suppression of IGF-1 receptor in mice (mammals) produces mutants that live longer than controls and resist stress better. Longevity (less than invertebrates) Physiologic Actions All Normal: growth, food intake, physical activity, development, reproduction, basal metabolism Resistance to stress Serum IGF-1 Tolerance to glucose, tissue IGF-1 Mechanisms of action Energy metabolism from aerobic to anaerobic Free radical accumulation 4)

13. Suppression of fat specific insulin receptor (FIRKO) Longevity (18-25%) Metabolism Protection against insulin resistance Fat mass Obesity protection Insulin/IGF-1 pathways Free radical accumulation Rodents deficient in GH,GH-R, PL, TSH Sensitivity to insulin Longevity (40-60%) (with delayed aging) IGF-1 Insulin Postnatal growth Body size Food intake Blood glucose levels Puberty Reproduction

14. Figure 2.3: Common causes of death by age in the United States (also look 3.7) Pathology: abnormal function leading to disease * COPD: Chronic Obstructive Pulmonary Disease ** Disease of Kidney

15. Recent approaches challenge the inevitability of functionpathology by grouping the aging processes into three categories: 1.Aging with disease and disability 2.Usual aging, with absence of overt pathology but presence of some declines in function 3.Successful or healthy aging, with no pathology and little or no functional loss

16. Such a grouping of aging processes: 1.De-emphasizes the view that aging is exclusively characterized by declines in functional competence & health 2.Refocuses on the substantial heterogeneity among old persons 3.Underscores the existence of positive trajectories (i.e., without disability, disease, major physiological decline) 4.Highlights the possible avoidance of many, if not all, the diseases and disabilities usually associated with old age

17. Assessment of Physiological Age in Humans Physiological age depends on Physiologic competence: good to optimal function of all body systems & Health status: absence of disease Physiological age may or may not coincide with chronological age

18. Laboratory Values in Old Age: 1.Most values unchanged (e.g. hepatic, coagulation, electrolytes, renal, thyroid, blood count, etc.) 2.Some values decreased (e.g. HDL in women) 3.Some values increased (e.g. LDL in men, glucose) **See Table 3.2**

19. Secrets to Long Life