Cell Differentiation and Aging

1. 1
Mitochondria and Aging
Amir Hamza
Student ID: B19008
Major: Biochemistry
College of Medicine

2. 2
 An organelle found in large numbers in most cells, in which the biochemical
processes of respiration and energy production occur. It has a double membrane,
the inner layer being folded inward to form layers (cristae).
What is Mitochondria?

3. 3

4. 4
Function of Mitochondria…

5. 5

6. 6
Mitochondrial dysfunction during aging and age-related disorders.

7. 7
Figure 2. The crosstalk or coordination between the two opposing processes i.e., selective
elimination of damaged or dysfunctional mitochondria by mitophagy and generation of newly
synthesized mitochondria by mitochondrial biogenesis is pivotal for the maintenance of
mitochondrial energy and cellular homeostasis in response to various physiological and
environmental cues
Crosstalk between mitochondrial biogenesis and mitophagy.

8. 8Figure 1. Stem Cells Exhibit Asymmetric Mitochondrial Inheritance

9. 9
Bidirectional Signaling between the Nucleus and Mitochondria
Figure 2. Both directions of this signaling paradigm appear intimately linked to longevity

10. 10
Parkin-Dependent Mitophagy

11. 11
Mitochondria as Regulators of the Innate Immune Response

12. 12
Mitochondria as Regulators of Organismal Aging

13. 13
Figure 1. Immune activation by mtDNA release through both intracellular and extracellular pathways.
The innate immune system has at least
three sensors for detecting mtDNA
• Extracellular: TLR9
• Intracellular: NLRP3

14. 14
 The age-dependent decline
in mitophagy might provide
the mechanism to explain
the known…
• Interrelationship between
increased ROS,
• Decreased bioenergetic
capacity, and
• Age-dependent functional
decline.
Figure 2. Aging impairs mitophagic removal of
stressed mitochondria.
Role of mitochondria in aging

15. 15
Figure 3. A range of quality control
mechanisms exist to deal with stress
in the mitochondria.
Role of mitochondria in aging

16. 16
Mitophagy in neurodegeneration and aging.

17. 17
 Signals downstream of the DDR cause
mitochondrial dysfunction via p38MAPK and
TGFβ,
 SASP and chronic inflammation via
NF-κB and C/EBPβ and may directly or
indirectly suppress autophagy and mitophagy.
 SASP and mitochondrial dysfunction feedback
to maintain and enhance DNA damage at
least partly via ROS generation.
 Many potential interactions within the network
(indicated by red arrows) are still insufficiently
understood. See text for further details.
Fig. The cell senescence signalling network.

18. 18
Exercise could be prescribed as medicine in
the treatment of 26 different diseases
including
• psychiatric diseases,
• neurological diseases,
metabolic diseases,
• cardiovascular diseases,
• pulmonary diseases,
• musculo-skeletal disorders, and
• cancer Fig. 1 Multifaceted beneficial role of exercise through
change in mitochondrial dynamics
Exercise and mitochondrial biogenesis

19. 19
Fig. 2 Exercise-stimulated activation of AMPK and downstream signaling that
stimulates mitochondrial biogenesis and mitophagy flux.
AMPK activation in exercise physiology

20. 20
Modulation of Drp1, Mfn1/2, and Opa1 activity by exercise
through post-translational modification.

21. 21
Modulation of Drp1 activity in pathological conditions.

22. 22

23. 23