3. telomere erosion 

chronic inflammation accelerates cell division, increases oxidative stress
and degrades telomers

senescence can be prematurely triggered by oxidative stress, DNA damage, and gene mutations.

senescent cells do play a role in our bodies...

free radicals (ROS) damage DNA.
telomeres are VERY vulnerable to oxidants.

quick review of DNA's job...

1. DNA Methylation:
as we age, chemical tags called methyl groups (CH4)
 are added or removed from your DNA.
predictable patterns of methylation/demethylation
can be tracked that
add up to a person's "epigenetic clock"
​ =
a measurement of one's biological age versus
 chronological ageation

the science of aging:
part 3

back to telomeres...

environmental/lifestyle factors cause epigenetic proteins which regulate DNA function to loosen and rearrange incorrectly 

why??

1. Chaperone Inefficiency:
molecular chaperones (ex: heat/cold shock proteins) help to fold newly made proteins or refold misfolded ones. their activity decrease with age, leading to a backlog of improperly folded proteins

2. Impaired Degradation Machinery:
damaged proteins are primarily cleared by the ubiquitin-proteasome system (proteases) and autophagy but proteasome activity drops and autophagic clearance becomes sluggish in aging cells.
harmful, insoluble protein aggregates to build up in tissues such as like neurons.

3. Ribosome aging:
the ribosome is the organelle that translates the DNA/RNA into the protein. age-related changes in this the efficiency of translation causes
ribosomes to pause and increases the production of defective proteins.

cellular senescence contributes to tissue dysfunction, weakens the immune system, increases vulnerability to age-related conditions
​(cardiovascular disease and metabolic disorders)

what  to do??

...
what's a telomere? 

3. Chromatin Remodeling:
the wear and tear from normal cellular activity
 loosens our chromatin packaging which changes gene accessibility and causes cells to misread their code. this can lead to cellular senescenc.n

6. reduction in proteostasis

5. epigenetic modification

 epigenetic modifications are fluid (unlike our pre-set DNA code). the epigenetic age of cells can be adjusted by:
natural intervention: diet, sleep, exercise, calorie restriction, and stress-reduction protocols  decrease biological age

medical intervention: specific transcription factors have been used in animal models to reprogram the aging epigenome. 

reduced proteostasis is directly linked to
 protein-misfolding diseases like Alzheimer's, Parkinson's, and Huntington's. 

...
... the progressive shortening of telomeres 

so how are epigenomic changes related to aging?

​3 ways...

​​or

        proteostasis = protein homeostasis
                                               it's the balance between:
             1. assembling amino acids into their correct order in a chain to
                     make a protein
             2. folding of this chain of amino acids into its correct shape
                       (the shape of the protein determines its function!)
             3. moving the protein to where it is needed in or out of the cell
             4. degrading the protein when it is no longer useful or viable

shorten = AGING

2. Histone Modification:
DNA is tightly wrapped around proteins called histones. changes in the structure of these histones are can cause genes to be incorrectly turned on or off.

1. Exercise and Physical Activity
aerobic and resistance training naturally upregulates autophagy.
exercise activates molecular pathways which helps prevent
inflammation and protects your cells from accumulating toxic proteins.

2. Diet and Fasting Protocols
what and when you eat significantly influences your proteostasis.
intermittent fasting or mild caloric restriction triggers pathways that initiate cellular repair and up-regulate molecular chaperones so
 proteins fold properly.
anti-inflammatory foods that are nutrient-dense and a plant-rich diet provides antioxidants that neutralize oxidative stress. Diets high in polyphenols (found in berries, tea, and dark chocolate) and omega-3 fatty acids (found in fish or walnuts) support cell function.

3. Cellular Stress Management
 chronic stress generates free radicals that cause proteins to misfold

but too many = :(

4. senescence

a. the cell undergoes cell death (apoptosis) to prevent genomic instability.

 senescence is a state of irreversible cell-cycle arrest.
old or damaged cells stop dividing but remain metabolically active. too many of these
 "zombie" cells
leads to chronic inflammation, and aging.

we discussed topics 1 & 2 in past meetings. 

today, we'll explore topics 3 through 6

b. the cell becomes senescent

...
as cells divide, the DNA replication machinery cannot fully copy the very tip of the chromosome.  this natural attrition acts as a biological clock
which determines the 
cells lifespan and prevents runaway cellular growth leading to cancer

a. our genomes generally loses overall methylation over time, leading to genomic instability
b. specific, clustered regions of DNA tend to become heavily methylated which can repress genes that handle DNA repair and tumor suppression
c. the lifespan accumulation of methylation changes are influenced by environmental factors, lifestyle, and underlying genetic regulation

what  to do??

 the progressive reduction in proteostasis is a primary hallmark of aging leading to the accumulation of misfolded, damaged proteins. this drives age-related decline and neurodegenerative diseases. 

quick review of your epigenome...

1. mitochondrial dysfunction
2. genomic instability
​3. telomere erosion
4. cell senescence
5. epigenomic modifications
6. reduction in proteostasis

 changes to your epigenome contribute more to aging than DNA mutations. 

when telomeres erode to a critically short threshold, a DNA damage response is triggered...

so we already knew the key to managing the negative effects of aging are
diet
exercise

and

chronic stress comtrol.

but now we know
WHY! 

DNA polymerase (the enzyme that assembles new DNA) is unable to replicate the 3' end of the DNA strand.

what  to do??

Senescent cells do not go dormant...they secrete a toxic mix of pro-inflammatory cytokines, chemokines, and growth factors that
 damages healthy tissue and triggers other cells into senescence.

although telomeres shorten naturally, the rate of erosion can

vary based on environmental and lifestyle factors. Studies suggest that excessive attrition can be slowed down by:
1. consuming a diet rich in antioxidants, fiber, and omega-3 fatty acids.  foods like legumes, nuts, fruits, and vegetables are
positively associated with telomere maintenance.
2. managing stress...chronic stress leads to higher levels of cortisol and oxidative stress which accelerates erosion.
3. avoiding exposure to environmental pollutants and habits like smoking which dramatically increases oxidative stress