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    Chapter 2

    Molecules, Cells

    and Theories

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    Molecules, Cells and Theories

    Overview

    Biomolecules

    The Cell

    Theories of Aging

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    Cells contain anaqueous solution,with 1000s of solutes:

    single atoms (electrolytes)

    small molecules large molecules

    SUPER KEY CONCEPT

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    Water

    Composition of Tissue (by weight)

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    FOUR Major Classes o f

    Biomolecu les?

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    FOUR Major Classes of

    Biomolecules

    proteins

    carbohydrates

    lipids

    nucleic acids

    MOST respons ib le fo r LIFE?

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    Water

    Life by Purves, 7th Ed. Figure 3.2

    Composition of Tissue (by weight)

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    Water

    Life by Purves, 7th Ed. Figure 3.2

    Composition of Tissue (by weight)

    SIX basic nu tr ien ts?

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    Water

    Life by Purves, 7th Ed. Figure 3.2

    Composition of Tissue (by weight)

    HOW do large biomo lecu les

    get to BE so large?

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    Large biomolecules arepolymers(molecular chains).

    KEY CONCEPT

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    You ARE what you eat, but

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    food monomers new polymers

    hydro lys is

    DIGESTION ANABOLISM

    (within gut) (within cells)

    You ARE what you eat, but

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    There are TWO TYPES of

    metabolismin the cell:

    anabolism

    ? ? ?

    catabolism ? anabolism

    KEY CONCEPT

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    CHON

    Biomolecules Primarily Consist

    of FOUR Different Atoms

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    FOUR Major Classes of

    Biomolecules

    proteins

    carbohydrates

    lipids

    nucleic acids

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    1. Structural Proteins: form structural

    components of the cell.

    2. Enzymes: speed and regulate

    biochemistry.

    Two Main Types

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    KEY CONCEPT

    The 3D shape of proteins isESSENTIAL for their function

    it allows it to INTERACT with a

    specific molecule.

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    A Polypeptide

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    What causes a protein to fold?

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    Folding occurs SPONTANEOUSLY,

    based on the amino acid sequence.

    Environmental factorsalso affect the

    conformation.

    Key Concept

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    Proteins Have FOUR Levels

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    Proteins Have FOURLevels

    of Structure

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    Protein Conformation

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    Making proteins is ANABOLIC.

    Where does the ENERGY

    come from???

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    FOUR Major Classes of

    Biomolecules

    proteins

    carbohydrates

    lipids

    nucleic acids

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    Carbohydrates

    sugars and sugar polymers

    monosaccharides

    polysaccharides

    FUNCTIONS: energy ANDstructure

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    Glucose

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    Polysaccharides

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    FOUR Major Classes of

    Biomolecules

    proteins

    carbohydrates

    lipids

    nucleic acids

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    Lipids

    molecules that are mostly H and C

    Functions:

    1) energy source (fats)

    2) structural (phospholipids)3) cholesterol and its derivatives

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    Triglyceride

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    Saturated?

    Unsaturated?

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    Phospholipid

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    Hydrophilic AND Hydrophobic

    Fig 5.13

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    Cholesterol

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    Nucleic Acids

    nucleotides 4 different ones

    polynucleotide

    two types

    Functions: information storage (polynuc leot ides)

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    Nucleic Acids

    nucleotides 4 different ones

    polynucleotide

    two types

    Functions: information storage (polynuc leot ides)

    energy source (a nucleot ide)

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    Nucleic Acids

    nucleotides 4 different ones

    polynucleotide

    two types

    Functions: information storage (polynuc leot ides)

    energy source (a nucleot ide: ATP)

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    ATP

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    DNA RNA protein

    WHY?

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    DNA RNA protein

    WHY?

    How many X genes do we have??

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    The Central Dogma

    transcription translation

    a gene mRNA polypeptide

    DNA RNA protein

    replication

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    RECAP

    1. Cells are constructed for FOUR main

    types of biomolecules.2. The most complex are proteins, which

    provide both structure and function.

    3. Genes(DNA) provide the instructions

    to make all proteins.

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    The Central Dogma

    a gene mRNA polypeptide

    DNA RNA protein

    replication

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    The DNA is Organized

    It is not just one long strand!

    It is organized into distinct units

    called CHROMOSOMES.

    How are the TERMS related?

    RELATIONSHIPS

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    Chromatin(size = large)

    All genetic material in the nucleus

    3 x 109base pairs

    The DNA from ONE cell stretched out wouldbe about 6 feet long.

    RELATIONSHIPS

    RELATIONSHIPS

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    RELATIONSHIPS

    CHROMOSOME(size = medium)

    DNA/PROTEIN structures carrying GENES

    1 x 106-7nucleotides per chromosome 23 PAIRS in humans

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    The essential

    GENOME

    no pairs!

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    GENE(size = small)

    nucleotide sequence of DNAthat controls ONE

    hereditary characteristic of an organism.

    encodes an RNA molecule (Ex: mRNA)

    ~ 1 x 104 5 x 105bp per gene

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    ATATGCATGCAGATATACGTACGTCT

    CHROMOSOME

    GENE

    CHROMATIN

    RELATIONSHIPS

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    Heterochromatin

    Tightly PACKED chromatin, notavailable for gene expression.

    M l l C ll d Th i

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    Molecules, Cells and Theories

    Overview

    Biomolecules

    The Cell

    Theories of Aging

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    Cell Membrane

    A barrier to maintain the cells internal

    chemistry.

    Made up of:1) phospholipids

    2) diverse proteins

    Also provides broad FUNCTIONALITY:Ex: transport, receptors, joining cells

    C

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    Cell Membrane

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    Mitochondria

    Use sugar, fat and protein tomake ATP.

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    Once an ancient BACTERIAL CELL!

    Orig in of Mi tochondr ia?

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    Once an ancient BACTERIAL CELL!

    Have their own DNA!

    Orig in of Mi tochondr ia?

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    Allow for the MANUFACTURE and

    SECRETION of biomolecules.

    ER and Golgi

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    Lysosome

    Life by Purves, et.al., 7th Ed. Figure 7

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    Gives SHAPE/SUPPORT as well as

    additional functionality to the cell.

    Cytoskeleton

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    Cytoskeleton

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    Our Multicellularity

    = ?

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    1. Cells + other structure.

    2. Also: empty space!

    Multicellularity

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    Intercellular Materials

    1. Amorphous Materials: vary in theirwater/protein content

    Ex: blood

    Ex: cartilage

    Ex: bone

    2. Fibers

    a) Collagen: fibers twisted into thick cables

    Ex: tendons, ligaments, bone

    b) Elastin: more flexible

    Ex: dermis skin, ears

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    WHY do cells d iv ide?

    1) Growth/development

    2) Repair/regeneration

    3) Reproduction

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    Cells Reproduce byMitosis

    1. Chromosomes are duplicated by DNAreplication.

    2. Pulled apart by the cytoskeleton,which also pinches cell in half.

    C ll C l

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    Cell Cycle

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    Do ALL cel ls div ide?

    The frequency of mitosis

    depends on cell type.

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    G0

    Frequency of Mitosis Depends

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    1) Continuous

    2) Based on need

    3) Rare/never

    Go applies to 2 and 3

    Most human cells are in Go

    Frequency of Mitosis Depends

    on Cell Type

    K C t

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    Replicating a chromosomes ENDS

    (telomeres) requires a special enzyme:

    Telomerase

    Without this enzyme, a cells ability toproliferate is limited!

    Key Concept

    K C t

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    The cells of humans and otheranimals CANNOT DIVIDEINDEFINITELY in culture.

    The # of rounds of cell division

    characteristic of that cell type is theHayflick Limit.

    It decreases as an organism ages!

    Key Concept

    Molecules Cells and Theories

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    Molecules, Cells and Theories

    Overview

    Biomolecules

    The Cell

    Theories of Aging

    Key Concept

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    Numerous theories have been

    proposed to explain biological aging.

    = hypotheses

    overlap

    aging may involve several/all/(none?)

    Key Concept

    Why consider aging from an

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    y g g

    evo lut ionary standpo int?

    Nothing in biology makes senseexcept in the light of evolution.

    --1973 Essay byTheodosius Dobzhansky

    E l ti

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    Evolution

    The change in the genetic compositionof a population from generation to

    generation, that over time brings aboutnew species.

    Occurs by mutation.

    Proceeds by natural selection.

    survival of the fittest

    = reproductive success!

    Why isnt aging ELIMINATED

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    y g g

    by evolu t ion?

    An organism is no longer neededfollowing successful reproduction!

    = selfish gene theory (Dawson)

    Limited resources may have resultedin a BALANCE b/w the genes forSURVIVAL (defense/repair) and genesfor REPRODUCTION.

    Three Criteria for Valid Theory

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    1) The changes addressed mustoccur COMMONLY in all members

    of the species.2) The process must be

    PROGRESSIVE.

    3) The process must lead to ORGANDYSFUNCTIONS that ultimatelylead to failure of organ/system.

    Three Criteria for Valid Theory

    Three Main Groups of Theories

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    1) Aging results from WEARING OUTof an organ/system.

    2) Aging results from nonreversibleCHEMICAL CHANGES within cellsthat alter its functioning.

    3) Aging is programmed by aBIOLOGICAL CLOCK, located in asingle center or in each cell.

    Three Main Groups of Theories

    Theories of Aging

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    Theories of Aging

    1. Genetic

    2. Rate of Living

    3. Free Radical

    4. Mitochondrial

    5. Clinker

    6. Cross-Linkage

    7. Immune Deficiency

    8. Wear and Tear

    Genetic Theories

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    Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation

    4. Faulty DNA Repair

    5. Error Catastrophe

    Death Gene Theory

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    Death Gene Theory

    A SET OF GENES activates late in life,

    and tells the body to deteriorate anddie.

    Cou ld genes invo lved in age-related

    diseases BE the death genes?

    Telomere Theory

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    Telomere Theory

    Shortening of telomeresaffects the

    expression of certain genes.

    Ex: through heterochromatin unwinding

    May occur at DIFFERENT RATES indifferent tissues!

    Somatic Mutation Theory

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    Somatic Mutation Theory

    Harmful factors may INJURE GENES.

    Ex: radiation, toxic chemicals, freeradicals

    Simplistic, but may be combine/contribute to free radical and faulty DNArepair theories.

    Faulty DNA Repair Theory

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    Faulty DNA Repair Theory

    DNA damage is repaired EARLY in life.

    Over time, the repair mechanisms

    begin to fail.

    Error Catastrophe Theory

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    Error Catastrophe Theory

    Damage to RNA and protein result in

    biological aging.

    EX: protein synthesis proteins, leadingto accumulation of mistakes

    Disproven!

    RECAP: Genetic Theories

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    RECAP: Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation4. Faulty DNA Repair

    5. Error Catastrophe

    Which involves a programmed

    BIOLOGICAL CLOCK?

    RECAP: Genetic Theories

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    RECAP: Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation4. Faulty DNA Repair

    5. Error Catastrophe

    Which invo lve(s) non reversib le

    CHEMICAL CHANGES in cel ls?

    RECAP: Genetic Theories

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    RECAP: Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation4. Faulty DNA Repair

    5. Error Catastrophe

    Which invo lve(s ) WEARING

    OUT of an organ/system?

    RECAP: Genetic Theories

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    RECAP: Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation4. Faulty DNA Repair

    5. Error Catastrophe

    Which has been DISPROVEN?

    RECAP: Genetic Theories

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    RECAP: Genetic Theories

    1. Death Gene Theory

    2. Telomere Theory

    3. Somatic Mutation4. Faulty DNA Repair

    5. Error Catastrophe

    Which has been reworked

    in to *FR and FDR?

    Theories of Aging

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    Theories of Aging

    1. Genetic

    2. Rate of Living

    3. Free Radical

    4. Mitochondrial

    5. Clinker

    6. Cross-Linkage

    7. Immune Deficiency

    8. Wear and Tear

    Rate of LivingTheory

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    Metabolic rateis DIRECTLY related to the

    rate of aging, and INVERSELY related to

    life span.Animals can use only a FIXED AMOUNT

    of calories/oxygen in their lifetime.

    DISPROVEN: by comparison of different

    organisms, etc. May combine/

    contribute to *FR and mito *FR theories!

    Free Radical

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    Free Radical

    An atom/molecule with an ODD number

    of esan unpaired electron (*FR).

    Ex: *O2, *OH

    highly reactive! occur naturally (Ex: in the presence

    of oxygen, high glucosevia ROS)

    implicated in more than 60 disordersEx: heart disease, cancer, Alz dis

    damages lipids, proteins, and DNA

    eliminated by antioxidants

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    Free Radical Theory

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    Free Radical Theory

    FREE RADICAL DAMANGE is a OR themain reason for biological aging andrelated diseases.

    TO:

    lipids: membrane permeability,mitochondrial energy production,

    atherosclerosis, more *FR proteins: disrupts enzymes, structure

    DNA: slows cell division, promotescancer

    Mitochondrial Theory

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    MitochondrialTheory

    Mitochondrial activity AND damagecause aging. Ties FREE RADICALTHEORY to mitochondria!

    Ex: mitochondria are a main source of*FRs!

    Ex: *FRs damage mitochondria

    Ex: Radiation/chemicals damage mito Ex: damage accumulates over time

    Ex: mito have DNA

    Ex: mito DO NOT have DNA repair

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    Clinker Theory

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    ClinkerTheory

    Waste products accumulate in cellsover time. (Cellular garbage theory)

    Simplistic, but may be combine/

    contribute to C-L theory.

    Ex: accumulation of misfoldedproteins.

    Cross-Linkage Theory

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    Cross Linkage Theory

    Post-translational modification toproteins resulting in irreversiblechanges to their structure, occurringover time. Affects flexibility/functioning/

    size of tissues and body parts. Broadeffects: skin, arteries

    Due to: free radicals and glucose

    Glycation

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    Glycation

    Covalent joining of a sugar(Ex: glucose) to a protein via

    particular amino acids.

    without an enzyme

    (vs. glycosylation)

    Cross-Linkage Theory

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    Cross Linkage Theory

    Post-translational modification toproteins resulting in irreversiblechanges to their structure, occurringover time. Affects flexibility/functioning/

    size of tissues and body parts. Broadeffects: skin, arteries

    Due to: free radicals and glucose

    Esp. affects diabetics!Ex: enzymes

    Ex: collagen (~ 30% of bodys proteins!)

    Ex: agg of proteins leads to neurodeg disease

    Immune Deficiency Theory

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    Immune Deficiency Theory

    Over time, immune system begins todamage YOUR tissues(autoimmunity).

    Wear and Tear Theory

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    Wear and Tear Theory

    An accumulation of injuries adverselyaffects the tissues/bodies.

    Which theory is co rrect?

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    Which theory is co rrect?

    Aging may be due to aCOMBINATION of these or still

    other causes!

    some more/less important?

    a chain reaction cause/effect?