Epigenetic changes

DNA methylation

addition of a methyl group (-CH3) to cytosine bases

Base pairs in DNA coding

adenine+thymine (A-T) and cytosine+guanine (C-G)

how do methyl groups alter gene expression w/o changing the DNA sequence?

methyl groups cover genes, therefore, genes turn “off”

increased methylation at gene promoters =

transcriptional repression (less expression)

reduces methylation =

greater gene accessibility (more expression)

hypomethylation

genomic instability; every single gene is turned on

hypermethylation

silencing of repair, metabolic, and regenerative genes; genes are off and increase of disease

Aging is characterized by ______ and ______

hypomethylation and hypermethylation

epigenetic is the study of what?

of how our behaviors and environmental factors (diet, stress, exercise) that cause changes that affect the way genes work without altering the underlying DNA sequence

histone

protein structure to organize and DNA around

nucleosome

groups of histones wrapped together

histone modifications

chemical changes to histone proteins that regulate how tightly DNA is wrapped around nucleosomes, controlling gene accessibility and transcription

histone acetylation

• adding acetylene groups (-COCH3) to histone tails by histone acetyltransferases (HATs)

• loosens chromatin structure (more access to activate genes)

• increased gene transcription, particularly metabolic and stress response genes

histone methylation

• adding methyl groups (-CH3) to histone tails by histone methyltransferases (HMTs)

• repress transcription by wrapping up the DNA around histones, limiting access, and the antithesis of acetylation (less genetic activation)

• provides long-term regulatory stability of gene expression patterns

functional role of chromatin remodeling

• determines whether transcription factors can access genes

• enables rapid gene activation or repression in response to physiological stress

  • critical for cell differentiation, repair, and adaptation

how aging affects the epigenome (4 things)

• global DNA hypomethylation → genomic instability (all genes on)

• site-specific hypermethylation at regulatory and repair genes (genes off)

• loss of youthful histone marks (denotations of efficient high function cells) → altered chromatin structure

• increased transcriptional noise (loss of precisions in gene expression)

drivers of epigenetic drift/alterations (4 things)

• time-dependent replication errors

• chronic inflammation and oxidative stress

• metabolic stress and mitochondrial dysfunction

• environmental and lifestyle exposures

why epigenetic alterations matter for aging?

aging is not only genetic damage, but progressive dysregulation of gene expression

how much of aging is genes v.s lifestyle?

about 20-30% genetics and 70-80% lifestyle

what happens during chromatin remodeling (ATP-dependent)?

ATP provides energy during chromatin remodeling:

• sliding nucleosomes along DNA to expose certain genes (protein has easier access to DNA)

• removing or replacing histones to change how DNA is packaged (more or less accessible)

• exposing or blocking regulatory DNA regions

  • exposed DNA: proteins can bind and potentially active a gene

  • blocked DNA: proteins can’t easily bind, potentially reducing gene expression

what is chromatin remodeling?

is the process of changing how tightly DNA is packaged so that genes can be turned ON or OFF

• open: loosely packed DNA; genes are more accessible

• closed: tightly packed DNA; genes are less accessible

result of epigenetic alterations change w/ aging

cells gradually lose the ability to tightly regulate gene expression