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

Drawing of Great Basin Bristlecone Pine (Pinus longaeva). According to

dendrochronologists, these trees have been been documented to live up to 5000 years.

Table 3-1 Physiologic Correlates with Longevity

INDEX STUDIED CORRELATION

Body weight Direct

Brain/ body weight Direct

Basal metabolic rate Inverse

Stress Inverse

Reproductive function/Fe cundity Inverse

Length of growth period DirectEvolution Uncertain

Figure 3.3: The

heterogeneity of the elderly

population as illustrated by scores in

a hypothetical

test.

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 yearsOLD OLD: 85+ years

CENTENARIANS: 100+ years

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

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 lifespanhermaphrodite19,000 genes959 cells

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

3)

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

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-1Tolerance to glucose, tissue IGF-1

Mechanisms of action•Energy metabolism

from aerobic to anaerobic• Free radical accumulation

4)

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

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

Recent approaches challenge the inevitability of function pathology 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

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

Assessment of Physiological Age in Humans

Physiological age depends onPhysiologic competence: good to

optimal function of all body systems

&Health status: absence of disease

Physiological age may or may not coincide with chronological age

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**

Secrets to Long Life