Ex2 L8 - Mitochondrial Dysfunction in Aging

Question 1

The mitochondria is…

Answer 1

the major site of cell energy metabolism (ATP synthesis)

Question 2

ATP is ——- and it provides energy because…

Answer 2

adenosine triphosphate, energy is stored in phosphate bonds, which break to release the energy

Question 3

ATP is used to do —— in cells such as:

Answer 3

work, such as:
- active transport
- contraction

Question 4

ATP is made in:

Answer 4

mitochondria (oxidative phosphorylation)
and cytoplasm (glycolysis)

Question 5

What are the important points about glycolysis?

Answer 5

• does not consume O2 (therefore is not a source of reactive oxygen species
• does not produce CO2
• produces ATP rapidly but inefficiently (2 ATP per glucose)

Question 6

What are the important points about oxidative (aerobic) ATP production?

Answer 6

• consumes O2
• produces CO2
• produces ATP efficiently but slowly (each pyruvate from glucose makes over 30 ATP)

Question 7

——— from ——– can undergo oxidative/aerobic ATP production.

Answer 7

glucose, fatty acids, and amino acids
from carbohydrates, lipids, and proteins

Question 8

Oxidative/aerobic ATP production involves both —— and ——-.

Answer 8

the citric acid cycle (TCA)
the electron transport chain

Question 9

Reactive oxygen species are produced during…

Answer 9

Normal O2 metabolism - oxidation-reduction reactions in the ETC produce reactive oxygen species as a normal byproduct
OR
Exposure to pollutants, tobacco, radiation, etc.

Question 10

In the past it was believed that reactive oxygen species were…

Answer 10

the direct cause of aging

Question 11

Small amount of reactive oxygen species are…

Answer 11

normal/expected and needed for certain functions

Question 12

How do reactive oxygen species relate to aging?

Answer 12

• as age increases, the amount produced increases and ability to neutralize them decreases
• they accumulate, causing oxidative stress
• oxidative stress causes tissue injury and inflammation that leads to aging and age-related disease

Question 13

What are the three main types of reactive oxygen species?

Answer 13

superoxide, hydrogen peroxide, and hydroxyl radicals

Question 14

What does superoxide mutase do?

Answer 14

turn superoxide into hydrogen peroxide

Question 15

What does peroxidase do?

Answer 15

turns hydrogen peroxide into water

Question 16

An imbalance of —— and —— lead to ———

Answer 16

imbalance of free radicals (ROS) and antioxidants leads to oxidative stress

Question 17

Antioxidants function by ——-, not by ———

Answer 17

by neutralizing ROS, not by preventing ROS formation

Question 18

What is inflammaging?

Answer 18

increased activation of the immune system with age (mitochondria play a role)

Question 19

Although inflammaging increases activation of the immune system, it is still bad becuase:

Answer 19

the activation is dysregulated and therefore not active at the appropriate times
chronic inflammation leads to chronic activation of the signaling pathways

Question 20

How do cytokines relate to successful aging?

Answer 20

circulating levels of inflammatory cytokines are inversely correlated with successful aging because chronic inflammation leads to chronic activation of signaling pathways

Question 21

5 things caused by inflammaging are:

Answer 21

• DNA damage
• proinflammatory cytokines
• oxidative stress
• immunosenescence
• autophagy

Question 22

What is immunosenescence?

Answer 22

immune system slows down and stops functioning

Question 23

What is the Danger Theory?

Answer 23

molecules from mitochondria acts as DAMPs and trigger an immune response that is similar to the response to a pathogen

Question 24

How do senescent cells relate to the Danger Theory?

Answer 24

• they release molecules that trigger immune response called DAMPs (damage-associated molecular patterns)
• response is similar to response to dangerous pathogens

Question 25

How do mitochondria relate to the Danger Theory?

Answer 25

- mitochondria are derived from bacteria, evidenced by their circular DNA in plasmids - normally this DNA is buried deep in the mito where the immune system doesn't see it - but when the mito starts to lose function, they get leaky and some plasmid DNA escapes - this DNA looks just like bacterial DNA, so the immune system is activated against it - in this way, the mito DNA acts as a DAMP and causes an immune response like you would get to a pathogen

Question 26

How is mitophagy triggered?

Answer 26

- triggered by accumulation of ubiquitinated proteins on damaged or stressed mitochondria (large proteins that flag the mito for lysosomes) - they are degraded by lysosomes instead of the entire cell dying

Question 27

How does mitophagy change with age?

Answer 27

- mitophagy declines with age - leads to increases ROS and DAMPs - leads to oxidative stress and inflammation - that coupled with reduced bioenergetics (less good at making ATP) - results in age related disease

Question 28

Mitochondrial stress is not always bad becuase:

Answer 28

- ROS are important for antioxidant production - exercise stimulates ROS production AND antioxidant production (which can be inhibited by oral antioxidants) - ROS are important for wound healing