Cellular Aging

A. Introduction

1. The cell is the basic structural and functional unit of life

2. Four basic components

a. Cell (plasma) membrane

b. Organelles

c. Cytoplasm

d. Inclusions

B. Cell (plasma) membrane

1. Bilayer of phospholipids

a. Hydrophilic phosphate “heads”

b. Hydrophobic fatty acid “tails”

2. Integral vs. peripheral proteins

3. Carbohydrate groups and their roles

4. Selectively permeable

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C. Organelles

1. Nucleus

a. Control center of the cell

b. Houses DNA

c. Genes transcribed into mRNA(process of transcription)

d. mRNA moves into cytoplasm

e. mRNA is translated into protein at a ribosome (process of translation)

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C. Organelles

2. Endoplasmic reticulum

a. Network of membranous tubules

b. Smooth vs. rough ER

c. Functions

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i. Synthesis of proteins destined for secretion

ii. Steroid synthesis

iii. Detoxification

iv. Storage

C. Organelles

3. Ribosomes

a. Granules of protein and rRNA (ribosomal RNA)

b. Free-floating in cytoplasm or attached to endoplasmic reticulum (rough ER)

c. Become associated with mRNA during translation, giving rise to a new protein

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C. Organelles

4. Golgi apparatus (complex)

a. Stacks of flattened membranous sacs

b. Function in packaging materials destined for secretion

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C. Organelles

5. lysosomes

a. Membrane-bound vesicles

b. Contain strong, non-specific protein-digesting enzymes

c. Present in all cells; very prevalent in phagocytes and macrophages

d. Functions

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C. Organelles

6. mitochondria

a. Double membrane-bound

b. Inner membrane has multiple folds that contain “respiratory” enzymes

c. Functions in production of energy (ATP) from food sources

d. More prevalent in highly metabolic cell types

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C. Organelles

7. Centrioles

a. Paired cylinder-shaped arrays of microtubules that lie at right angles to each other

b. Involved in cell division, giving rise to a network of tubules called the spindle fibers

c. Spindle fibers involved in redistribution of chromosomes to daughter cells

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C. Organelles

8. Cytoskeleton

a. 3-D network of microfilaments and microtubules

b. Functions

i. Maintain cell shape

ii. Aid in cell organization

iii. Transport within the cell

iv. Cell division

v. Cellular movement

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D. Validity of cell culture findings

1. Normal cells in culture lose their mitotic ability

a. They don’t die (HeLa cells)

b. But they do age like normal cells in the body

2. Mix old cells with young cells – old stop mitosis first

3. Conditioned medium experiments

4. Fibroblasts from progeria patients

5. Transplant studies

6. Cells in vitro exceed the abilities of cells in vivo

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E. Specific cellular changes during aging

1. Cellular aging is generally thought to be influenced by changes in cell functions that:

a. Alter protein synthesis

b. Reduce the efficiency of DNA repair

c. Decrease enzymatic activity

2. All the specific cellular changes that have these effects aren’t known

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E. Specific cellular changes during aging

3. Membrane changes

a. Alterations in transport of nutrients, ions, amino acids, and proteins

b. Loss of fluidity due to structural changes

i. Plasma membrane – changes in permeability

ii. Endoplasmic reticulum

iii. Mitochondria – decreased metabolic activity

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E. Specific cellular changes during aging

4. Nuclear changes

a. All changes in nuclear function would be expressed in altered protein synthesis

b. Altered enzymes and structural proteins would lead to altered cell functions

c. Specific changes include:

i. Increased DNA damage

ii. Decreased efficiency of DNA repair processes

iii. Increased cross-linking of DNA, leading to inaccessible genes

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E. Specific cellular changes during aging

5. Cytoplasmic changes

a. Increased volume coupled with decreased DNA synthesis

b. Build-up of lipofuscin

6. Ribosomal changes

a. Decreased total ribosomal RNA (rRNA)

b. Decreased number of ribosomes

c. Result = decreased protein synthesis

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E. Specific cellular changes during aging

7. Mitochondrial changes

a. Lipofuscin may be produced by old mitochondria

b. Reduced inner membrane folds

c. Decreased number of total mitochondria

d. Increased dysfunction resulting from free radicals

e. Results = decreased ATP production

8. Lysosomal changes

a. Less efficient in removing cell garbage

b. Damaged lysosomes leak their enzymes, causing cell damage/death

F. Take home messages

1. Most of the data comes from cell culture work

2. Many of the changes involve synthesis of or activities of proteins (enzymatic and structural)

3. Specific changes that are known to occur include:

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a. Membrane alterations

b. Increased DNA damage

c. Decreased DNA repair

d. DNA cross-linking

e. Lipofuscin accumulation

f. Decreased mitochondria

g. Inefficient lysosomes

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