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Contents:

1. GENETICS IN AGING

1.1. GENETIC APPROACHES TO AGING RESEARCH

1.1.1. GENETIC LOCI IN HUMAN OF POTENTIAL RELEVANCE TO THE PATHOBIOLOGY OF AGING

1.1.2. COMPARATIVE GERONTOLOGIC APPROACH

1.1.2.1. HOW DO MANY SPECIES OF BIRDS MANAGE TO ACHIEVE THEIR UNUSUAL LONGEVITIES?

1.1.3. PROMISING EXPERIMENTAL APPROACHES

1.2. INCREASED RESISTANCE TO STRESS, ASSURES LONGEVITY

1.2.1. THE EXISTENCE OF GERONTOGENES

1.2.2. MAJOR GERONTOGENE MUTANTS

1.2.3. GERONTOGENES IN THE EVOLUTION OF SENESCENCE

1.2.4. FUTURE OF AGING RESEARCH

1.3. NONLINEARITY OF THE AGING PROCESS

1.3.1. NONLINEARITY OF YEAST AGING

1.3.2. CHANGE AS THE CAUSE OF AGING

1.3.3. EVIDENCE FOR CHANGE AT THE LEVEL OF THE INDIVIDUAL

1.3.4. EPIGENETIC STRATIFICATION

1.4. GENETIC BASIS FOR REPLICATIVE CELLULAR SENESCENCE OF HUMAN CELLS

1.4.1. GENETIC BASIS FOR CELLULAR SENESCENCE

1.4.2. PATHWAYS TO CELLULAR SENESCENCE

1.4.3. CELLULAR SENESCENCE IN TELOMERASE POSITIVE HAMSTER CELLS

Chapter 1 References

2. MITOCHONDRIAL BIOENERGETICS AND REACTIVE OXYGEN SPECIES IN DEGENERATIVE DISEASES AND AGEING

2.1. MITOCHONDRIAL BIOENERGETICS AND FREE RADICALS

2.2. MITOCHONDRIA

2.3. mtDNA MUTATIONS IN DEGENERATIVE DISEASE

2.4. MITOCHONDRIAL IN COMMON DISEASES

2.5. MITOCHONDRIAL DECLINE AND mtDNA MUTATIONS IN AGING

2.6. INCREASE SOMATIC mtDNA MUTATIONS IN DEGENERATIVE DISEASES

2.7. MOUSE MODELS TO EXPLAIN USEFUL MUTATIONS

2.8. MOUSE MODELS OF DEGENERATIVE DISEASES AND AGING

2.9. ANT1-DEFICIENT MICE

2.10. MnSOD DEFICIENT MICE

2.11. MODEL FOR MITOCHONDRIAL DISEASE AND AGING

Chapter 2 References

3. TELOMERES AND TELOMERASE IN THE REGULATION OF HUMAN CELLULAR AGING

3.1. FUNCTIONS OF TELOMERES

3.2. MECHANISM FOR TELOMERE SHORTENING

3.3. RELATIONSHIP BETWEEN TELOMERE SHORTENING AND CELLULAR SENESCENCE

3.4. EVIDENCE THAT INHIBITION OF TELOMERE SHORTENING EXTENDS CELLULAR LIFESPAN

3.5. ARE CELLS EXPRESSING TELOMERASE "NORMAL"?

3.6. TELOMERASE AS A PRODUCT TO EXTEND CELL LIFESPAN

3.7. CLOSING ON TELOMERASE

Chapter 3 References

4. ENDOGENOUS DNA DAMAGE, MUTAGENESIS AND AGING

4.1. 8-OXODEOXYGUANINE

4.2. ABASIC SITES

4.3. EXOCYCLIC DNA ADDUCTS

4.4. ORGAN-SPECIFIC MUTATION ACCUMULATION

4.4.1. INFLUENCE OF DEFECTS IN CELL CYCLE CHECKPOINTS AND DNA REPAIR

4.4.1.1. THE TP53 GENE

4.4.1.2. THE XPA NUCLEOTIDE EXCISION REPAIR GENE

4.5. CONCLUSIONS AND FUTURE PROSPECTS

Chapter 4 References

5. DNA DAMAGE AND REPAIR

5.1. SEQUENCE-SPECIFIC DNA DAMAGE BY IRON-MEDIATED FENTON REACTIONS

5.1.1. FENTON REACTIONS, DNA DAMAGE AND AGING

5.2. GENES AND ENZYMES FOR THE REMOVAL OF OXIDATIVE DNA BASE DAMAGE

5.2.1. GENES FOR DNA GLYCOSYLASES IN E. coli AND HUMAN CELLS

5.2.2. ENDONUCLEASE III AND HOMOLOGUES IN EUKARYOTIC CELLS

5.2.3. THE HUMAN ENZYME FOR 8-OXOGUANIN REMOVAL

5.2.4. BROAD SPECIFICITY DNA GLYCOSYLASES IN THE REPAIR OF OXIDATIVE DNA DAMAGE

Chapter 5 References

6. PROTEIN SYNTHESIS, POST-TRANSLATIONAL MODIFICATIONS AND AGING

6.1. ACCURACY OF PROTEIN SYNTHESIS

6.2. TRANSLATIONAL CHANGES DURING AGING

6.2.1. INITIATION OF TRANSLATION

6.2.2. POLYPEPTIDE CHAIN ELONGATION

6.3. POST-TRANSLATIONAL MODIFICATIONS

6.3.1. PHOSPHORYLATION

6.3.2. ADP-RIBOSYLATION

6.3.3. METHYLATION

6.3.4. OXIDATION

6.3.5. GLYCATION

6.3.6. DEAMIDATION, RACEMIZATION AND ISOMERIZATION

6.3.7. OTHER MODIFICATIONS

Chapter 6 References

7. SIGNALLING AND INTERVENTION

7.1. MELANOCYTE AGING IN VIVO AND IN VITRO

7.2. ACTIVATION OF THE cAMP SIGNALING PATHWAY BY α-MSH AND CHOLERA TOXIN: A TOPSY-TURVY RESPONSE

7.3. THE CELL CYCLE: CYCLIN-DEPENDENT KINASE INHIBITORS (CDK-1) AND TRANSCRIPTION FACTORS OF THE E2F FAMILY

7.4. EFFECT OF AGE ON DNA REPAIR

7.5. EFFECT OF DIETARY RESTRICTION ON DNA REPAIR

7.6. EFFECT OF AGING AND DIETARY RESTRICTION ON GENE-SPECIFIC REPAIR

Chapter 7 References

8. AGE RELATED DISEASES; HELICASES AND AGING

8.1. HELICASES

8.2. SEGMENTAL PROGEROID SYNDROMES

8.2.1. XERODERMA PIGMENTOSUM

8.2.2. COCKAYNE SYNDROME

8.2.3. TRICHOTHIODYSTROPHY

8.2.4. BLOOM SYNDROME

8.2.5. WERNER SYNDROME

8.2.6. X-LINKED A-THALASSEMIA: MENTAL RETARDATION SYNDROME AND JUBERG-MARSIDI SYNDROME

8.3. HELICASE DISORDERS AND ORDINARY AGING

8.4. ALZHEIMER'S DISEASE: MOLECULAR CONCEPTS AND THERAPEUTIC TARGETS

8.4.1. EXTRACELLULLAR RELEASE OF Aβ

8.4.2. INTRACELLULAR Aβ ACCUMULATION

8.4.3. GENES RESPONSIBLE FOR AD

8.4.4. FORMATION OF TOXIC Aβ FIBRILS

8.4.5. INFLAMMATORY EFFECTOR PHASE

8.4.6. CLOSING ON AD

Chapter 8 References