Hallmarks of aging and mitochondrial dysfunction Flashcards
What are the 9 hallmarks of aging?
- telomere attrition
- genomic instability
- epigenetic alterations
- mitochondrial dysfunction
- cellular senescence
- stem cell exhaustion
- altered cellular communication
- deregulated nutrient sensing
- loss of proteostasis
what makes a hallmark, a hallmark of aging?
- should manifest during normal aging?
- experiment aggravation should accelerate aging
- experimental amelioration should retard the normal aging process and hence increase healthy lifespan
what is mitohormesis
Mitohormesis is a process wherein reactive oxygen species (ROS) produced by mitochondria at a low concentration act as signaling molecules to initiate a cascade of cellular events that ultimately protect the cells from harmful effects. Low activation > high inhibition
How does dietary restriction effect aging?
dietary restriction acitvates Sirt1 and AMPK. Sirt1 activates PGC1 alpha and that inhibits aging. AMPK inhibits mTOR that is supposed to enhance aging
What are the causes of genomic instability?
- exogenous: chemical, biological agents, physical and radiation
- endogenous: DNA replication errors and spontaneous hydrolytic reactions
How is hayflick limit linked to telomere attrition?
Hayflick limit states that a cell can divide only so much, the cause of this is telomere attrition. Everytime it divides the telomere shortens and that causes the cells to eventually have apoptosis
What are the 3 types of epigenetic alterations?
- DNA methylation
- post-translational modification of histones
- chromatin remodelling
how does deregulated nutrient sensing have an effect on aging?
it activates GH > IGF-1> PI3K > Akt. Akt inhibits Foxo that is supposed to inhibit aging. Akt also activates/enhances mTOR that enhances aging.
What does the antagonistic pleiotropy theory state?
It hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge.
What does the disposable soma theory state?
The disposable soma theory focuses on mechanistic trade-offs between repair and reproduction through a shared resource pool. in easy words> growth and repoduction favours over maintenance and repair
What does the mutation accumulation theory state?
accumulation of a wide range of alleles with late deleterious effects over the generations with little or no check.
What is selection shadow?
It states that selection pressures on an individual decrease as an individual ages and passes sexual maturity, resulting in a “shadow” of time where selective fitness is not considered.
How does mitochondria produce ROS?
During ATP production, an electron can be leaked causing superoxide anion. this happens the most in I and III
Why is mtDNA so prone to damage?
- not protected by nuclear membrane or histone proteins
- does not have introns so lesions occur more in coding DNA
- directly exposed to ROS due to ATP production
- Mitochondria contain DNA-polymerase gamma, this is more error prone than DNA-polymerase III.
What are the defenses against mtROS and damage?
- antioxidants (catalase converts H2O2 to H2O)
- repair systems for damaged, proteins, DNA and oxidised lipids
- mitochondrial degradation and turnover
