Ch. 24 Aging & Senescence

Question 1

• Accumulation of DNA damage throughout life

* Loss of DNA repair mechanisms accelerate aging

Answer 1

Genomic instability

Question 2

Lack of telomerase

Shorter telomeres are associated with increased mortality at young age

Answer 2

Telomere Attrition

Question 3

Chromatin remodeling
•Heterochromatin formation

mRNA miRNA

Answer 3

Epigenetic alterations

Question 4

Decreased synthesis of chaperone proteins

Protein degradation (lysosome & proteasome) decrease with age

Answer 4

Loss of protein homeostasis

Question 5

Anabolic pathways

dietary restriction

Sirtuins signal nutrient scarcity & promote cell survival & catabolism
Lopez

Answer 5

Deregulated nutrient sensing

Question 6

•May stimulate proliferative & survival signals
•Less efficient at generating ATP as we age
TOXINS

Answer 6

Mitochondrial dysfunction

Question 7

• Decreased in hematopoiesis with age
• Cell cycles decrease in stem cells in aged
• Due to more DNA damage & overexpression of INK4A (cyclin inhibitor)

Answer 7

Stem cell exhaustion

Question 8

Increase in inflammation (AKA ‘inflammaging’)

•Enhanced activation of NF-kB, senescent cells produce more inflammatory cytokines,

Answer 8

Altered intracellular communication

Question 9

Senescent cells do not re-enter growth cycle

Still metabolically active, just do not replicate any more

Answer 9

Cellular Senescence

Question 10

inflammatory cytokines

Elevated cytokines

liver disease, degenerative disc disease, cancer

Answer 10

Senescence & Disease