Ex2 L8 - Mitochondrial Dysfunction in Aging Flashcards
The mitochondria is…
the major site of cell energy metabolism (ATP synthesis)
ATP is ——- and it provides energy because…
adenosine triphosphate, energy is stored in phosphate bonds, which break to release the energy
ATP is used to do —— in cells such as:
work, such as:
- active transport
- contraction
ATP is made in:
mitochondria (oxidative phosphorylation)
and cytoplasm (glycolysis)
What are the important points about glycolysis?
- 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)
What are the important points about oxidative (aerobic) ATP production?
- consumes O2
- produces CO2
- produces ATP efficiently but slowly (each pyruvate from glucose makes over 30 ATP)
——— from ——– can undergo oxidative/aerobic ATP production.
glucose, fatty acids, and amino acids
from carbohydrates, lipids, and proteins
Oxidative/aerobic ATP production involves both —— and ——-.
the citric acid cycle (TCA)
the electron transport chain
Reactive oxygen species are produced during…
Normal O2 metabolism - oxidation-reduction reactions in the ETC produce reactive oxygen species as a normal byproduct
OR
Exposure to pollutants, tobacco, radiation, etc.
In the past it was believed that reactive oxygen species were…
the direct cause of aging
Small amount of reactive oxygen species are…
normal/expected and needed for certain functions
How do reactive oxygen species relate to aging?
- 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
What are the three main types of reactive oxygen species?
superoxide, hydrogen peroxide, and hydroxyl radicals
What does superoxide mutase do?
turn superoxide into hydrogen peroxide
What does peroxidase do?
turns hydrogen peroxide into water
An imbalance of —— and —— lead to ———
imbalance of free radicals (ROS) and antioxidants leads to oxidative stress
Antioxidants function by ——-, not by ———
by neutralizing ROS, not by preventing ROS formation
What is inflammaging?
increased activation of the immune system with age (mitochondria play a role)
Although inflammaging increases activation of the immune system, it is still bad becuase:
the activation is dysregulated and therefore not active at the appropriate times
chronic inflammation leads to chronic activation of the signaling pathways
How do cytokines relate to successful aging?
circulating levels of inflammatory cytokines are inversely correlated with successful aging because chronic inflammation leads to chronic activation of signaling pathways
5 things caused by inflammaging are:
- DNA damage
- proinflammatory cytokines
- oxidative stress
- immunosenescence
- autophagy
What is immunosenescence?
immune system slows down and stops functioning
What is the Danger Theory?
molecules from mitochondria acts as DAMPs and trigger an immune response that is similar to the response to a pathogen
How do senescent cells relate to the Danger Theory?
- they release molecules that trigger immune response called DAMPs (damage-associated molecular patterns)
- response is similar to response to dangerous pathogens
How do mitochondria relate to the Danger Theory?
- 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
How is mitophagy triggered?
- 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
How does mitophagy change with age?
- 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
Mitochondrial stress is not always bad becuase:
- 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
