Topic07 - Epigenetics of Aging Flashcards
What are the two main theories of aging?
- Programmed theory of aging
2. Damage or Error theory of aging
State the subcategories of the Programmed theory of aging
- Programmed longevity
- Endocrine theory
- Immunological theory
State the subcategories of the Damage/Error theory of aging
- Wear and tear theory
- Rate of living theory
- Cross-linking theory
- Free-radicals theory
- Somatic DNA damage theory
Define programmed longevity
The programmed longevity theory poses aging as a result of a sequential switching on and off of certain genes, explaining aging as a primary disorder instigated by inner coordination and control mechanisms.
Define senescence
Senescence is defined as the combination of processes of deterioration which follow the period of development. In other words, it is the process by which a cell loses its ability to divide, grow, and function
Define cellular senescence
The state at which a cell in the body can no longer divide.
What are SASPs?
Senescent cells can assume a special secretory form (SASP) in which they release various chemical signals that harm the health of nearby cells.
Briefly discuss the epigenetic changes involved in the formation of senescent cells.
- Histone deacetylation occurs
- macroH2A enriches histones
- Histone methylation occurs
In short, heterochromatin is irreversibly formed at senescence-associated heterochromatin foci (SAHF). As proliferation-related genes are located within SAHF, proliferation is halted in senescent cells.
Briefly discuss DNA methylation in terms of aging
DNA methylation is globally reduced, but local DNA methylation increases.
Hypomethylation of LINEs and SINEs increases transposition, resulting in decreased DNA stability
Define the term epigenetic clock
An epigenetic clock is a biological clock to help in predicting the aging process
Define the term hazard ratio
A hazard ratio is the probability of an event in some experimental group at a given time, divided by the probability of the same event in a control group.
A hazard ratio of 1 means there is no difference, a hazard ratio of 2 means there is twice the risk
When does age acceleration slow?
Around adulthood (20 yrs)
What is the percentage of age acceleration in babies?
100%
List the three biological clocks.
- Horvath’s clock
- Hannum’s clock
- Levine’s clock
State the epigenetic changes monitored by the Horvath’s, Hannum’s and Levine’s clock
DNA methylation-based biomarkers
State the tissue(s) involved in Hannum’s clock
Whole blood tissue (single tissue)
State the tissue(s) involved in Horvath’s clock
It is a multi-tissue age estimator, taking into account 51 types of tissues.
Discuss the performance of Hannum’s clock versus Horvath’s clock
Hannum’s clock performs better in predicting biological age, while Horvath’s clock performs better in predicting lifespan
Briefly describe Levine’s clock
Levine’s clock takes into account the weighted average of 10 clinical characteristics, regressed on DNA methylation levels in blood.
State the clinical characteristics used in constructing Levine’s clock
- Chronological age
- Albumin
- Creatine
- Glucose
- C-reactive protein levels
- Lymphocyte percentage
- Mean cell volume
- RBC distribution width
- Alkaline phosphatase
- WBC count
Briefly explain the heterochromatin-loss model of aging
This model suggests that the loss of heterochromatin that accompanies aging leads to changes in global nuclear architecture and the expression of genes residing in those regions.
This causes transcriptional and genomic instability.
An abnormal chromatin state causes a feedback loop, causing more epimutations.
The heterochromatin-loss model is currently outdated. TRUE or FALSE?
TRUE. It is updated with the heterochromatin-reorganisation model.
Briefly explain the heterochromatin-reorganisation model
Heterochromatin marks are redistributed during aging (e.g. heterochromatin formation at SAHF).
Decondensation of heterochromatin occurs alongside condensation of euchromatin
Briefly discuss the effect of core histone protein loss in aging
The loss of core histone proteins have been shown to be a cause of aging in yeast.
Notably, all genomic regions showed transcriptional up-regulation, due to increased access of transcription machinery to DNA sequences.
