Transcript Chapter 2 Theories of Aging

Theories of Aging
A. Mechanisms of aging
1. Humans can be subdivided
into 3 biological components.
a. cells that divide and produce new cells as long
as the person lives
b. cells that are incapable of dividing after
final differentiation
c.
noncellular substances located between cells
2. All components are subject to physiological
controls within the body.
Theories of Aging
A. Mechanisms of aging
3. Early hypotheses explained aging based on these
subdivisions
a. vigor declines as a result of changes in mitotic cells
b. vigor declines as a result of loss of postmitotic cells
c.
vigor declines as a result of changes in
intercellular materials
4. Early hypotheses were too simplistic
Theories of Aging
B. General theories of aging
1. To be valid, an aging theory must meet three criteria
a. aging changes must occur commonly in all members
of a given species
b. process must be progressive with time
c.
process must produce changes that cause organ
dysfunction, leading the organ or its system to
ultimately fail
Theories of Aging
B. General theories of aging
2. All theories fall into 1 of 3 groups
a. cellular damage or wearing out
b. nonreversible cellular changes
c.
biological clock
3. Individual theories
aging by program theory
gene theory
gene mutation theory
cross-linkage theory
free radical theory
cellular garbage theory
accumulation-of-errors theory
wear-and-tear theory
autoimmune theory
Theories of Aging
C. Aging by program theory
1. Each species has its own average longevity
2. Aging is programmed into each species
3. So where is this biological clock?
a. hypothalamus
b. thymus gland
c.
individual cell types
i.
total number of mitoses
ii.
RNA and enzyme production
iii.
physiological dysfunction
Theories of Aging
D. Gene theory
1. Programmed aging is due to harmful genes
a. normal harmful genes that become active
b. normal good genes that become go bad (mutations)
2. Theory suggests that lifespan is inherited
Theories of Aging
E. Gene mutation theory
1. Mutations can alter normal cellular function
2. Accumulation of mutations lead to malfunction
3. What is DNA?
4. Cells have mechanisms that
allow them to repair DNA
Theories of Aging
F. Cross-linkage theory
1. Denatured proteins are irreversibly altered
2. Denaturation is caused by cross-links between
peptide strands within a protein or between protein
strands
3. With age comes new cross-links, leading to
irreversible protein structural changes, leading to
altered protein functioning
Theories of Aging
F. Cross-linkage theory
4. Commonly affected body proteins include enzymes,
collagen (fibrosis), elastin, components of ground
substance, DNA
5. Advanced glycation end-products (AGEs)
glucose
2% aldehyde + proteins
cross-linked
98% lactone
--protein--sugar group--protein--
Theories of Aging
G. Free radical theory
1. Cellular chemicals with unpaired electrons
2. Formed as by-products of processes using oxygen
UV light
H2O ---> H. + .OH
3. Very unstable, reactng rapidly with other substances,
particularly proteins and saturated fats, altering
structure and therefore function (membranes, DNA)
4. Free radicals are self-propagating
Theories of Aging
G. Free radical theory
5. There is gradual accumulation of free radicals in cells
over time; once threshold is reached, they promote
changes associated with aging
6. What are antioxidants? Vitamins A, C, and E
2 O2. + 2H2+
superoxide
dismutase
catalase
H2O
H2O2
peroxidase
H2O
Theories of Aging
H. Cellular garbage theory
1. Aging cells accumulate substances as a result of
normal metabolism
-- free radicals, histones, aldehydes, lipofuscins
2. Lipofuscins – yellow-brown pigments, inert, strongly
cross-linked molecules (THE aging pigment?)
3. Theory suggests that gradual accumulation of inert
cell garbage, along with reactive substances,
interferes with normal function and contributes to
aging
Theories of Aging
I. Accumulation-of-errors theory
1. Protein synthesis involves a complex series of
sequential steps
amino acid chain
tRNA
tRNA +
amino acid
mRNA
ribosome
DNA
Transcription
Translation
Posttranslational
Modification
Theories of Aging
I. Accumulation-of-errors theory
2. Dysfunction and cell death result from accumulation of
random erros in protein synthesis (not mutations
3. Mainly affects enzymes, therefore metabolism, but
could also affect structural proteins
4. BUT, older cells synthesize proteins properly; perhaps
the problem lies in posttranslational modification of
proteins
Theories of Aging
J. Wear-and-tear theory
1. Each animal (each cell?) has a specific amount of
metabolic energy available to it
2. Rate at which energy is used determines lifespan
3. Experimental evidence
4. Related to Aging by Program and Accumulation of
Errors theories
Theories of Aging
K. Autoimmune theory
1. What is an antigen? What is an antobody?
2. With aging comes changes in the immune system
a. atrophy of thymus gland
b. slower responses of lymphocytes
c.
decreased production of interleukin-2
3. Autoimmune theories suggest that with age comes
decreased ability to recognize “self” from “nonself”
So what happens?
Theories of Aging
K. Autoimmune theory
4. New antigens
a. mutations yield altered proteins seen as foreign
b. Cells hidden during embryonic life appear later in life
5. Increase in autoimmune reactions
a. antibody structure becomes modified with aging, causing
them to acquire antigenic potential against normal cells
b. Ab-Ag complexes from previous normal responses cause
cumulative lesions characteristic of aging
c.
Medications may form complexes with body proteins that are
identified as foreign
Theories of Aging
L. Take home messages
1. No one theory explains growing old
2. Program theories help understand differences in aging
between species
3. Gene-based theories help understand differences
between individuals within a species
4. BUT, individuals vary in terms of diseases,
experiences, lifestyles, mutations, errors, and
accumulations. Therefore, individuals age at different
rates and in different ways.
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