1. Theories of Aging Mechanisms of aging
Humans can be subdivided into 3 biological components.
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.

2. Theories of Aging Mechanisms of aging
3. Early hypotheses explained aging based on these subdivisions
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

3. Theories of Aging B. General theories of aging
1. To be valid, an aging theory must meet three criteria
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

4. Theories of Aging B. General theories of aging
2. All theories fall into 1 of 3 groups
cellular damage or wearing out
b. nonreversible cellular changes
c. biological clock
3. Individual theories
aging by program theory cellular garbage theory
gene theory accumulation-of-errors theory
gene mutation theory wear-and-tear theory
cross-linkage theory autoimmune theory
free radical theory

5. Theories of Aging C. Aging by program theory
Each species has its own average longevity
2. Aging is programmed into each species
3. So where is this biological clock?
hypothalamus
b. thymus gland
c. individual cell types
total number of mitoses
ii. RNA and enzyme production
iii. physiological dysfunction

6. Theories of Aging D. Gene theory
Programmed aging is due to harmful genes
normal harmful genes that become active
b. normal good genes that become go bad (mutations)
2. Theory suggests that lifespan is inherited

7. Theories of Aging E. Gene mutation theory
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

8. Theories of Aging F. Cross-linkage theory
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

9. --protein--sugar group--protein--
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
98% lactone
2% aldehyde + proteins
--protein--sugar group--protein--
cross-linked

10. Theories of Aging G. Free radical theory
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

11. 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
superoxide dismutase
catalase
peroxidase
2 O2. + 2H2+
H2O2
H2O

12. Theories of Aging H. Cellular garbage theory
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

13. Theories of Aging I. Accumulation-of-errors theory
Protein synthesis involves a complex series of sequential steps
ribosome
mRNA
DNA
amino acid chain
tRNA
tRNA +
amino acid
Posttranslational
Modification
Transcription
Translation

14. 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

15. Theories of Aging J. Wear-and-tear theory
Each animal (each cell?) has a specific amount of metabolic energy available to it
Rate at which energy is used determines lifespan
3. Experimental evidence
4. Related to Aging by Program and Accumulation of Errors theories

16. Theories of Aging K. Autoimmune theory
What is an antigen? What is an antobody?
2. With aging comes changes in the immune system
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?

17. 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

18. 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.
end