Comparative and differential aging
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Comparative and Differential Aging. Chapter 3. Figure 3.2 : Comparison of the relationship of brain weight to life span in vertebrates. Figure 3.1 : Comparative Maximum Life Spans. **Detailed discussion of figure in the legend, pg. 26.

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

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Figure 3.1: Comparative Maximum Life Spans

**Detailed discussion of figure in the legend, pg. 26

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

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

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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

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Examples of ways in which the environment may influence the genome

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

  • 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

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C. Elegans genome

2 week lifespan


19,000 genes

959 cells

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.

Examples of ways in which environment influences the genome (cont.)


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Longevity genome6X


Resistance to stress;

Mechanisms of action

  • Energy metabolism from aerobic to anaerobic

  • Chaperons over-expression

Growth, Development, Metabolism

  • Free radical accumulation

  • In invertebrates, suppression of insulin/IGF-1 receptor and its homologue produces mutants that live longer than controls and resist stress better.

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Suppression of IGF-1 receptor in mice (mammals) produces mutants that live longer than controls and resist stress better.


(less than invertebrates)

Physiologic Actions

All Normal: growth, food intake, physical activity, development, reproduction, basal metabolism

Resistance to stress Serum IGF-1

Mechanisms of action

Tolerance to glucose, tissue IGF-1

  • Energy metabolism from aerobic to anaerobic

  • Free radical accumulation


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Longevity (18-25%) mutants that live

Longevity (40-60%)

(with delayed aging)

Metabolism Protection against insulin resistance

Sensitivity to insulin

Fat mass Obesity protection Insulin/IGF-1 pathways Free radical accumulation

Rodents deficient in GH,GH-R, PL, TSH

Suppression of fat specific insulin receptor (FIRKO)

IGF-1 Insulin Postnatal growth Body size Food intake Blood glucose levels Puberty Reproduction

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Figure 2.3 mutants that live: Common causes of death by age in the United States

(also look 3.7)

Pathology: abnormal function leading to disease






** Disease of


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Recent approaches challenge the inevitability of mutants that livefunction pathology by grouping the aging processes into three categories:

  • Aging with disease and disability

  • Usual aging, with absence of overt pathology but presence of some declines in function

  • Successful or healthy aging, with no pathology and little or no functional loss

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Such a grouping of aging processes: mutants that live

  • De-emphasizes the view that aging is exclusively characterized by declines in functional competence & health

  • Refocuses on the substantial heterogeneity among old persons

  • Underscores the existence of positive trajectories (i.e., without disability, disease, major physiological decline)

  • Highlights the possible avoidance of many, if not all, the diseases and disabilities usually associated with old age

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Assessment of Physiological Age in Humans mutants that live

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

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Laboratory Values in Old Age: mutants that live

  • Most values unchanged (e.g. hepatic, coagulation, electrolytes, renal, thyroid, blood count, etc.)

  • Some values decreased (e.g. HDL in women)

  • Some values increased (e.g. LDL in men, glucose)

**See Table 3.2**

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Secrets to Long Life mutants that live