Transcript lecture03

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 Correlat es with Longevity
INDEX STUDIED
CORRELATIO N
Body w eight
Direct
Brain/ body w eight
Direct
Basal me ta bolic rate
Inverse
Stre ss
Inverse
Reproduc t ive f unct ion/Fe cun dit y
Inverse
Length of growt h p eriod
Evo lut ion
Direct
Uncert ain
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 years
OLD 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
Examples of ways in which environment influences the genome (cont.)
3)
C. Elegans
2 week lifespan
hermaphrodite
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.
Longevity
6X
In invertebrates, suppression of insulin/IGF-1
receptor and its homologue produces mutants
that live longer than controls
and resist stress better.
Mechanisms of action
•Energy metabolism from aerobic
to anaerobic
•Chaperons over-expression
• Free radical accumulation
Consequences
Resistance to stress;
Growth,
Development,
Metabolism
Suppression of IGF-1 receptor in mice (mammals) produces mutants that
live longer than controls and resist stress better.
4)
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
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
Longevity (40-60%)
(with delayed aging)
Sensitivity to insulin
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 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
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