- Aging is characterized by a declining ability to respond to stress, increasing homeostatic imbalance, and higher risk of disease. It is a degenerative process with no positive features. - The main factors that act in the aging process include mitochondrial dysfunction, DNA damage and repair, cell cycle regulation, telomere shortening, and changes in transcription and translation. - Theories of aging include the molecular gene theory, cellular theories involving free radicals and apoptosis, and evolutionary theories such as antagonistic pleiotropy and mutation accumulation. Apoptosis is programmed cell death while necrosis is unregulated cell death from external factors like toxins.

1. CELL AGING

2. Introduction
• Aging is generally characterized by the declining ability to respond to
stress, increasing homeostatic imbalance and increased risk of aging-
associated diseases.
• Death is the ultimate consequence of aging.
• Differences in maximum life span between species correspond to
different "rates of aging".
• A degenerative process, only.
• Has no positive features.
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3. Cell
• The cell is the basic structural, functional, and biological unit of all
known living organisms.
Plant cell Animal cell
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4. Cell Aging
Mitochondria
DNA damage, repair and
mutagenesis
Gerontogenes and age related
diseases
Signal transduction
Cell cycle regulation and
cancer
Telomeres as molecular cell
clock
Age related transcription and
translation changes
The main factors acting in aging process
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5. Mitochondria
• Mitochondria are the main unit of chemical power supply in the cell.
• During the synthesis of macroergical bio-molecules free radicals are
being produced as the by-product.
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6. • Free radicals when released in large quantities cause intercellular
oxidative stress (e.g. oxidative damage of DNA, proteins and other
bio-molecules).
• Free radicals can result tissue degeneration by damaging
mitochondria genome and cause early apoptosis (programmed cell
death) through the damage of nuclear genome.
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8. Cell cycle regulation and cancer
• Cell cycle is regulated by different specific proteins.
• Lots of different proteins which regulate cell cycle, phase change
(cancer supressors, cyclins, and MAP kinases).
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9. • When these proteins are damaged by mutations cell cycle regulation
can be disturbed.
• Cells could die or become not controlled depending on the nature of
mutation- this could lead to cancer.
• Cell cycle regulation disorders leads to accelerated aging and/or cell
malignancy.
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11. Gerontogenes and age related diseases
• Genes concerned with pathological aging.
• When they are damaged organism ages much faster.
• These genes are named gerontogenes - aging genes.
• Genetic polymorphisms (determining individual's longevity) are
found.
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12. • The existence of longevity gene is still very real.
• Some age linked diseases are known in medical practice
(Werner's, Bloom's, Cocaine's syndromes, progery and
other).
• Patents had damaged various gerontogenes.
• It was observed that these genes encoded replication,
transcription and repair machinery components of the cell.
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13. Telomeres
• Telomeres are the terminal parts of eukaryotic chromosomes.
• The influence to aging of telomeres is highly discussed.
• They are called "molecular clock" of the cell. Cell division times are
correlated with telomere length.
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14. • After each cell division telomeres get shorter.
• When telomere shortens to the critical stage, the intensity of cell
division significantly decreases, and then cell differentiates and ages.
• Telomeres are persistent in the not aging cells: cancer and germ line.
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15. Age related transcription and translation changes
• The influence of transcription, translation and posttranslational
modification systems to the cell is not static but highly regulated.
• For example, when synthesized protein is modified incorrectly (wrong
phosphorylation) its function alters.
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16. • If protein function is important, appropriate intracellular processes or
regulation could be disturbed.
• Such errors lower vitality of organism and accelerate aging.
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17. Signal transduction
• Intracellular processes are accordant and rigorous; it means cell is
highly organized and integrated system.
• Information (signal transduction) and the regulation of bioprocess
are the main players in the development and the maintenance of this
system and aging.
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18. • When mutations or modification disturb proteins/genes of signal
systems, signal transduction and other bioprocesses proceed
abnormally.
• We should not forget that organism is integrated system and all
factors mentioned above act in-between with others.
• Mitochondrial metabolism process stimulates oxidative damage, but
each cell has repair systems defeating it (reparative systems,
apoptosis, etc.).
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20. Aging
• Aging is a natural process, living organisms are highly adapted to the
laws of nature, and senescent cells are being changed with juvenile.
• The existence of not differentiated stem cells in every living organism
has a deep meaning; they act as a depot in the regeneration of
damaged cells.
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21. Aging Theories
• Molecular Gene Theory
• Codon restriction
• Somatic mutation
• Gene regulation
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• Cellular theory
• Free radical theory
• Wear and tear theory
• Apoptosis
• Senescence
• Telomere loss (replicative senescence)
• Cellular stress (cellular senescence)

22. • System theory
• Rate of living theory
• Neuro endocrine theory
• Immunologic theory
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• Evolutionary theory
• Disposable soma
• Antagonistic pleiotropy
• Mutation accumulation

23. Molecular Gene Theories
• Codon restriction - Fidelity/accuracy of mRNA translation is impaired
due to inability to decode codons in mRNA.
• Error catastrophe - Fidelity of gene expression declines with age,
resulting in increased fraction of abnormal proteins.
• Somatic mutation - Accumulation of molecular damage, primarily to
DNA/genetic material.
• Dys-differentiation - Gradual accumulation of random molecular
damage impairs regulation of gene expression.
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24. • Gene regulation - Aging caused by changes in gene expression
regulating both aging and development. Gene expression protein
folding and activity
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25. Cellular Theories
• Free radical - Oxidative metabolism produces highly reactive free
radicals that subsequently damage protein and DNA. Mitochondrial
DNA Damage
• Wear and tear - Accumulation of normal injury – Glycooxidation
Theory of Aging (products from glucose with proteins + oxidation;
AGE (advanced glycation end products – Inflammation Theory of
Aging
• Apoptosis - Programmed cell death resulting from intrinsic damage
and genetically determined events or genome crisis.
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26. • Senescence - Phenotypes of aging are caused by an increase in
frequency of senescent cells. Senescence may be the result of
telomere loss (replicative senescence) or cell stress (cellular
senescence).
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27. System Theories
• Rate-of-living - Assumes a fixed amount of metabolic potential for
every living organism (live fast, die young).
• Neuroendocrine - Alterations in neuroendocrine control of
homeostasis results in age-related physiological changes also referred
as Neuroendocrine Theories of Aging.
• Immunologic – decline of immune function with age results in
increased incidence of disease also referred as Immunological Theory
of Aging
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28. Evolutionary Theories
• Disposable Soma - Somatic cells are maintained only to ensure
continued reproductive success, following reproduction the soma is
disposable. (life span theory)
• Antagonistic Pleiotropy - Genes that are beneficial at younger ages
are deleterious at older ages.
• Mutation Accumulation - Mutations that affect health at older ages
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29. Cell death
• For every cell, there is a time to live and a time to die.
• Two ways in which cells die
• they are killed by injurious agents
• they are induced to commit suicide
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30. • Apoptosis is a form of programmed cell death that occurs in
multicellular organisms. Biochemical events lead to characteristic cell
changes and death. These changes include blebbing, cell shrinkage,
nuclear fragmentation, chromatin condensation, chromosomal DNA
fragmentation, and global mRNA decay
• Necrosis is a form of cell injury which results in the premature death
of cells in living tissue by autolysis. Necrosis is caused by factors
external to the cell or tissue, such as infection, toxins, or trauma
which result in the unregulated digestion of cell components.
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31. Apoptosis
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cytoplasmic, nuclear
condensation
chromatin margination
membrane blebbing
cell implosion and formation of
apoptotic bodies
recognition and engulfment of apoptotic bodies by
phagocytic cells

32. Necrosis
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rapid membrane
permeabilization
swelling of the
cytoplasm
Swelling of the
nucleus
osmotic shock
release of intracellular
content

33. THANK YOU
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