Ferrari & Aprile: Lecture XXVII Flashcards
Molecular Mechanisms of Aging: Changes and mTOR singaling
What is the epigenetic clock?
describes how there is a complete change in the heterochromatin state that can be predicted analyzing DNA de-methylation
Describe the state of chromatin in young vs old:
young have a more condensed, repressive state
old have a more open, active, euchromatic state
What is the acetylation of the histone tail associated with?
different states in different organisms
What is nutrient sensing linked to?
the epigenetic landscape
What is cellular senescence strictly linked to?
epigenetic mechanisms
How is the epigenome influenced by metabolism?
it has been shown that caloric restriction can lead to rejuvenation
*animals tested also had a different landscape of both methylation and histone acetylation
Describe what could be seen in animals under caloric restriction:
downregulation of P16
repression of sirtuins
An increase in glycolysis in cells gives rise to ___.
accelerated aging phenotype
An overexpression of FAO (fatty acid oxidation) ___.
extends lifespan
Describe the interplay between the epigenome and mitochondria:
there is an interplay between the product of metabolism inside the mitochondria and how the product can control the nucleus’ different processes
What is NAD involved in?
it is a co-factor for sirtuins and a mitochondrial product that is used to control histone deacetylase
What does the increase of 𝛼-ketoglutarate give rise to?
activation of nuclear processes
What does an increase of ROS give rise to?
deregulation and changes of expression of mitochondrial genes
What does the genral loss of heterochromatin result in?
reactivation of transposons
What is inflammaging?
all the changes that give rise to the accumulation of pro-inflammatory cytokines the epigenetic changes can induce a pro-inflammatory phenotype in the cells
What is an example of premature aging syndrome?
Werner syndrome