Cellular Aging 2

www.youtube.
com/user/DrRabiulHaque
Dr. Rabiul Haque

Lecturer,
Department of Pathology,
Holy Family Red Crescent Medical College, Dhaka
www.youtube.com/user/DrRabiulHaque
Topics over view

Definition of Cellular Aging
Mechanisms
Role of DNA Damage
Role of Cellular Senescence
Role of Defective Protein Homeostasis
Role of Nutrient Sensing
Concept of Aging
Concept of Aging
Old age is a concept of longevity in human
beings.
Concept of Aging
beings.
Its consequences appear after reproductive
age.
Concept of Aging
beings.
age.
Average life expectancy approaching 80 yrs.
Concept of Aging
beings.
age.
Maximum lifespan of human is around 110
yrs.
Concept of Aging
beings.
age.
Maximum lifespan of human is around 110
yrs.
Fountain of Youth is still not found !
Concept of Aging
beings.
Its consequences appear after reproductive age.
Maximum lifespan of human is around 110 yrs.
We age because cells of our body age.
Concept of Aging
beings.
Its consequences appear after reproductive age.
Maximum lifespan of human is around 110 yrs.
We age because cells of our body age.
Aging is risk factor for many chronic diseases.
Definition
Definition
Cellular aging is the result of progressive
decline in cellular function and viability
Definition

caused by genetic abnormalities
Definition

and accumulation of cellular and molecular
damage
Definition

damage
Definition

damage
due to exposer to exogenous influences
Definition
Cellular aging is the result of progressive decline in
cellular function and viability

and accumulation of cellular and molecular damage
Ref: Robbins & Cortan Pathologic Basis of Disease 9 th
Edition
Stay Calm and Look At The

Teddy !
Definition
Cellular aging is the result of progressive decline in
cellular function and viability

and accumulation of cellular and molecular damage
Ref: Robbins & Cortan Pathologic Basis of Disease 9 th
Edition
Mechanisms
Mechanisms
DNA Damage
Mechanisms
DNA Damage
Cellular Senescence
Mechanisms
DNA Damage
Cellular Senescence
Defective Protein Homeostasis
Mechanisms
DNA Damage
Cellular Senescence
Defective Protein Homeostasis
Deregulated Nutrient Sensing
DNA Damage
DNA Damage
By endogenous agents (ROS)
DNA Damage
By exogenous agents (Physical, Chemical,
Biologic)
DNA Damage
By exogenous agents (Physical, Chemical,
Biologic)
e.g. Werner Syndrome ( Defective Helicase )
Cellular Senescence
Cellular Senescence
After fixed number of cell divisions, cells leave
cell cycle and become arrested in terminally

nondividing state.
Cellular Senescence
Cellular Senescence
Telomere Attrition
Cellular Senescence
Telomere Attrition
Tumor Suppressor Genes Activation
Telomere
Telomere
Short repeated sequences of DNA.
Telomere
Short repeated sequences of DNA.
Found at the both ends of linear
chromosomes.
Telomere
Telomere
Functions:
Telomere
Functions:
Ensures complete replication of the
chromosome ends.
Telomere
Functions:
Ensures complete replication of the
chromosome ends.
Prevents degradation and fusion of
chromosome ends.
Progressive Shortening of
Telomere
Telomerase
Telomerase
A specialized complex made up of RNA and
Protein.
Telomerase
Protein.
Maintains the length of Telomere.
Telomerase
Protein.
Adds nucleotides to the ends of chromosome.
Telomerase
Protein.
Present in germ cells, low level in stem cells,
absent in somatic cells.
Telomerase
Protein.
Present in germ cells, low level in stem cells,
absent in somatic cells.
Cancer cells can reactivate Telomerase
activity and therefore proliferate indefinitely.
Activating Tumor Suppressor

Genes

Genes
CDKN2A Locus

Genes
CDKN2A Locus
Encodes protein P16 or INK4a

Genes
CDKN2A Locus
Encodes protein P16 or INK4a
P16 controls part of cell cycle
(regulates progression from

G1 to S Phase of cell cycle)
Defective Protein
Homeostasis
Defective Protein
Normal protein homeostasis is maintained by:
Homeostasis
Defective Protein
Homeostasis
- Maintaining Correctly Folded
Conformations of
Proteins by Chaperons.
Defective Protein
Homeostasis
Conformations of
- Degradation of Misfolded Proteins:
Defective Protein
Homeostasis
Conformations of
- Autophagy-Lysosome System
Defective Protein
Homeostasis
- Maintaining Correctly Folded Conformations
of
- Autophagy-Lysosome System
- Ubiquitin-Proteosome System
Deregulated Nutrient
Sensing
Eating less increases longevity.
Sensing
Eating less increases longevity.
Sensing
Caloric restriction can increase life span.
Role of Insulin Like Growth Factor 1

Pathway
Growth Hormone Secretion from Pituitary
Gland causes production of Insulin and Insulin

Like Growth Factor 1 in many types of cells.

Pathway

IGF 1 mimics intracellular signaling by insulin.

Pathway


Pathway

Acts on multiple downstream targets: e.g.
AKT, mTOR ( mammalian Target of
Rapamycin ) etc.
Role of Sirtuins in Nutrient

Sensing

Sensing
NAD-dependent protein deacetylases.

Sensing
NAD-dependent protein deacetylases.
Increases longevity of cells.
Caloric Restriction Increases

Longevity By:

Longevity By:
Decreasing signaling intesity if IGF1 Pathway

Longevity By:
Decreasing signaling intesity if IGF1 Pathway

Increasing Sirtuins
( activates DNA repair enzymes, adapts the

cell to
caloric restriction )
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Cellular Aging 2

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Dr. Rabiul Haque

Topics over view

decline in cellular function and viability

decline in cellular function and viability

decline in cellular function and viability

decline in cellular function and viability

decline in cellular function and viability

cellular function and viability

Stay Calm and Look At The

cellular function and viability

cell cycle and become arrested in terminally

Activating Tumor Suppressor

Activating Tumor Suppressor

Activating Tumor Suppressor

Activating Tumor Suppressor

(regulates progression from

- Maintaining Correctly Folded Conformations

Caloric restriction can increase life span.

Role of Insulin Like Growth Factor 1

Gland causes production of Insulin and Insulin

Role of Insulin Like Growth Factor 1

Gland causes production of Insulin and Insulin

Role of Insulin Like Growth Factor 1

Gland causes production of Insulin and Insulin

Role of Insulin Like Growth Factor 1

Gland causes production of Insulin and Insulin

Role of Sirtuins in Nutrient

Role of Sirtuins in Nutrient

Role of Sirtuins in Nutrient

Caloric Restriction Increases

Caloric Restriction Increases

Decreasing signaling intesity if IGF1 Pathway

Caloric Restriction Increases

Decreasing signaling intesity if IGF1 Pathway

( activates DNA repair enzymes, adapts the

Thank you for watching this

Thank you for watching this

Thank you for watching this

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