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 Cellular Aging

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) Cellular Aging

C.Organelles 2.Endoplasmic reticulum a.Network of membranous tubules b.Smooth vs. rough ER c.Functions Cellular Aging 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 Cellular Aging

C.Organelles 4.Golgi apparatus (complex) a.Stacks of flattened membranous sacs b.Function in packaging materials destined for secretion Cellular Aging

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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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

Cellular Aging 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: Cellular Aging a.Membrane alterations b.Increased DNA damage c.Decreased DNA repair d.DNA cross-linking e.Lipofuscin accumulation f.Decreased mitochondria g.Inefficient lysosomes end