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Biochemistry II > Chapter 70: Aging > Flashcards

Chapter 70: Aging Flashcards

1
Q

Aging definition

A
  • Progressive deterioration of biological systems
  • Leads to increase in age-related mortality
  • Dependent on intrinsic and extrinsic factors
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2
Q

Average life expectancy in the U.S.

A
  • 81 years
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3
Q

Decrease in human physiological function with age shows

A
  • Linear decline in organ function with age
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4
Q

The Hayflick Phenomenon

A
  • Normal cells in fact have a finite replicative capacity which contributes to the aging process at the cellular level
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5
Q

In the Hayflick Phenomenon, at least one chromosome

A
  • Has lost a substantial part of its telomeres

- Cell stops dividing and dies

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6
Q

Only cells capable of overcoming the Hayflick Limit

A
  • Mutated cancer cells

- Cells expressing viral oncogenes

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7
Q

“Programmed” intrinsic cellular aging theories

A
  • Biological clock/ predetermined, sequential genetic “program” which governs the aging process
  • Follows a biological timetable
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8
Q

The somatic mutation hypothesis

A
  • Errors in DNA structure-aggressive environmental factors

- Not accurately repaired and accumulate over a lifetime

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9
Q

The umber of errors in the DNA of an aging cell is dependent on

A
  • The rate at which these errors occur and ability of the cell to repair them
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10
Q

Change in nucleotide structure involves

A
  • Methylation of cytosine moieties/residues

- Methylation has been shown to decrease with cell age

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11
Q

Changes in chromatin structure

A
  • Limit enzyme access to the DNA

- Causes problems with replication/repair

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12
Q

Telomere theory

A
  • In DNA synthesis after primer removal, the freshly replicated strand is sequentially shortened at the 5’-end
  • During differentiation telomerase becomes repressed
  • While dividing, the telomeres shorten until most chromosomes reach a critical minimum length of about 1.5 kbp, ‘‘crisis’’, death
  • Only a few cells escape “crisis” by mutations evoking telomerase activity
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13
Q

DNA damaging agents

A
  • Oxygen radicals
  • Advanced glycation end products (AGEs)
  • Mutagens
  • Ultraviolet light
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14
Q

Free radical theory of aging

A
  • Chemical species with a single unpaired electron

- Implicated in degenerative disorders, including cancer, atherosclerosis, cataracts, and neurodegeneration

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15
Q

“Biochemical bad boys” (free radicals)

A
  • Hydrogen peroxide

- Superoxide

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16
Q

Free radical damage can occur by

A
  • Repeated environmental exposure to ionizing radiation

- Progressive reduction of antioxidant defence mechanisms (superoxide dismutase/SOD)

17
Q

Free radicals can induce thousands of

A
  • Base modifications in mitochondrial and nuclear DNA per cell per day
18
Q

SOD findings (gerbil study)

A
  • SOD levels are directly related to life span in 20 different species
  • Longer-lived animals having higher levels of SOD
19
Q

SOD supplementation does not work because

A
  • It is broken down in digestion
20
Q

Other antioxidants correlated with extended life span

A
  • Vitamin C
  • Vitamin E
  • Beta-carotene
21
Q

SOD findings (fruit fly study)

A
  • Inserting extra copies of the SOD gene into fruit flies extends their average life span
  • Transgenic fruit flies, carrying extra copies of the gene for SOD, live 5-10% percent longer than average
22
Q

Mitochondria

A
  • The principal sites of energy production
  • Known to accumulate changes with age
  • Lysosomal pathway for removal may operate at reduced effectiveness with age
23
Q

Mitochondrial DNA

A
  • Damaged at a much greater rate than nuclear DNA during aging
  • Damage increases exponentially with age
  • Type II diabetes associated with defects in mitochondria
24
Q

Cellular changes with age

A
  • Irregular nuclei
  • Changes in mitochondrial shape
  • Decreased endoplasmic reticulum
  • Distorted Golgi apparatus
  • Accumulation of lipofuscin
25
Q

Advanced glycation end producs (AGEs)

A
  • Post-translational glycation of intracellular and extracellular proteins by glycation associated with aging
  • Production initially slow and non-enzymatic
26
Q

AGEs toughen tissues

A
  • May cause some of the deterioration associated with aging
27
Q

AGEs appear at younger ages in

A
  • People with diabetes, who have hyperglycemia
28
Q

Various biological activities of AGEs

A
  • Increase endothelial cell permeability
  • Bind to receptors stimulating secretion of cytokines
  • Quench of nitric oxide (inhibits vasodilation)
  • Enhance oxidative stress
  • Modify renal function
  • Oxidation of low-density lipoproteins
29
Q

Diabetic model of aging

A
  • Diabetic complications mimic the physiologic changes that can accompany old age
  • Diabetics have shorter life expectancies
30
Q

The body is able to defend itself against AGEs since

A
  • Macrophages bind, engulf, and digest them
31
Q

Degraded AGEs are

A
  • Ejected into the blood stream
  • Filtered by the kidneys and
  • Eliminated in urine
32
Q

AGE defense system is incomplete in the elderly, so

A
  • Level of AGEs increases

- Macrophages of the immune system become less active with advancing age

33
Q

Modification of hemoglobin by glycosylation

A
  • Provides an invaluable tool in the management of diabetic patients
34
Q

Three leading causes of death in people 75 to 84 years of age

A
  • Heart disease
  • Cancer
  • Cerebrovascular disease

Biochemistry II (5 decks)

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