1 Aging Flashcards
(28 cards)
Describe the Evolutionary theory of aging?
Aging occurs because of the decline in the force of natural selection.
What are the two mechanisms of the evolutionary theory of aging?
Mutation accumulation and antagonistic pleiotropy.
What is mutation accumulation?
Inherited or constitutional mutations that are expressed only after middle age, when the force of natural selection has become greatly attenuated.
What is antagonistic pleiotropy?
Gene variants enhance reproductive fitness early in life, but exhibit deleterious effects later in life.
What is the DNA damage theory of aging?
- DNA damage accumulates
- Leads to cellular alterations and disruption of tissue homeostasis
What are some of the effects of DNA damage aging?
Dysregulate gene expression & cells
Impair transcription
Cell cycle arrest
Mutations
Apoptosis
Two sources of DNA damage?
- Intrinsic sources
- Spontaneous chemical reactions
- ROS
- Extrinsic sources
- Chemicals and radiations
What are the three DNA repair pathways?
- Base excision repair
- Nucleotide excision repair
- Non-homologous end joining
What are the effects of age-related grad mitochondrial dysfunction and what causes it?
- Effects:
- Oxidative capacity and ATP production decrease
- Causes:
- Reactive oxygen species.
What mutation is responsible for Hutchinson-Gilford Progeria?
- Mutation in Lamin A gene
- Lamin A protein ( Progerin)
- Activates a cryptic splice donor site, which results in a isoform with 50 AA deletion.
What does Hutchinson-Gilford progeria result in?
- Defective Lamin A protein, retains farnesylation site (cant be removed)
- Progerin localizes incorrectly in nucleus
- Distorts nucleus and alters gene expression.
What causes werner syndrome?
Defect in gene coding for member of RecQ family of helicases - WRN
What does the defect in WRN do to cause werner syndrome?
- Unwinds and separates ds DNA
- Exonuclease
- Important in DNA replication and maintaining telomeres.
When cytosines are methylated they are?
Switched off, silent and condensed chromatin.
When a cytosine has been acetalyated it is?
Active (open) Chromatin
Switched on
Histone levels _____ during aging, this leads to _______.
- Decline
- More open chromatin structure leading to inappropriate transcription
How many base pairs are lost every cell division from a telomere?
30-150 bp
What is the function of telomerase?
What happens when it runs out in a cell?
Replace and add more bp to the telomere
Cell division stops after a delay, and cell is removed.
What occurs when the point is reached when protective loops cannot be formed.
Activation of cellular senescence or apoptosis
What happens to stem cells as we age?
AND
How to treat age related stem cell decline?
- Decline in number and type
- Treatment:
- Diversity maintenance (re add the prior variation)
- Clonal switch (switch the predominant stem cells for the less dominant one)
What are Sirtuins?
- Silent information regulator (SIR) genes
- Code for:
- NAD-dependent deacetylases
- NAD-dependent ADP-ribosyl transferases
- NAD-dependent deacylases
- Code for:
How many Sirtuins in mammals and where are they expressed?
- 7 in mammals
- SIRT1 in Euchromatin
- SIRT2 in Cytoplasm
- SIRT3,4,5 in Mitochondria
- SIRT6 Hetero-chromatin
- SIRT7 Nucleolus
What is the function of Sirtuins?
- Nuclear sirtuins act as transcriptional regulators to suppress gene expression.
- Deacetylate histones and other proteins
- Regulate telomere elongation
- Promote DNA repair by deacetylating repair enzymes.
Affect of Aging on Sirtuins?
- Mitochondrial function declines with age
- NAD+ levels decrease with aging
- Overexpression of some sirtuins slows aging in various organisms.
