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Cellular free radical defense

Compartmentalization:

Most oxidative metabolism and free radical production

• occurs at the inner mitochondrial membrane.

Protective enzymes

Several: SOD, catalase, glutathione peroxidase.

• 2H + O · O · --SOD-> O + H O

+ 2 + 2 2 2 2

H O + H O --CAT-> H O + O

2 2 2 2- 2 2

Concentrated in the mitochondria.

Antioxidant molecules

Evidence for the oxidative damage

theory

Correlation between species-specific

• levels of anti-oxidant defenses and

lifetime energy expenditure (Cutler,

1984).

Correlations stronger between

• mitochondrial (MnSOD) than

cytoplasmic (CuSOD, ZnSOD) defense

levels.

Free radical scavenging

systems

Evidence for the oxidative damage

theory

Comparison of mammals and birds:

• Rats (4 yr lifespan) and pigeons (35 yrs).

• Pigeon mitochondria leak only 30% of the

• free radicals than those from rat.

(Herrero and Barja, 1997).

Antioxidant EUK-134:

• Fed to C. elegans, increased mean and

• maximum lifespan 44%

(Giblin et al., 2003)

Activity in houseflies experiment

Raised houseflies in either:

• Large chamber, could fly (high activity)

• Low chamber, flies only walk (low activity)

• Low activity animals had longer mean and max

• lifespan, lower rate of lipofuscin formation.

Catalase activity high in young flies,

• decreases with age.

Peroxide levels (a measure of lipid oxidation)

• low in young flies, increase with age.

Sohal and Donato, 1978.

Testing the oxidative damage theory

1. Construct long-lived and short-lived

animals and then assay their

antioxidant defense levels.

2. Construct animals with genetically

altered levels of antioxidant defense

enzymes and then test for lifespan.

Testing the oxidative damage theory

1. Construct long-lived and short-lived

animals and then assay their

antioxidant defense levels.

2. Construct animals with genetically

altered levels of antioxidant defense

enzymes and then test for lifespan.

Effect of altered levels of SOD and

catalase in fly

See Orr and Sohal, 1994

• http://www.ncbi.nlm.nih.gov/entrez/query.

• fcgi?

cmd=Retrieve&db=pubmed&dopt=Abstra

ct&list_uids=8108730&query_hl=24&itool

=pubmed_docsum

Phillips et al., 2000

See

• http://www.ncbi.nlm.nih.gov/entrez/query.

• fcgi?

cmd=Retrieve&db=pubmed&dopt=Abstra

ct&list_uids=11113599&query_hl=21&ito

ol=pubmed_docsum

Metabolic rate declines with age

Biology of Aging, R. Arking, 3rd ed.


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DETTAGLI
Corso di laurea: Corso di laurea in biotecnologie
SSD:
Università: L'Aquila - Univaq
A.A.: 2010-2011

I contenuti di questa pagina costituiscono rielaborazioni personali del Publisher Atreyu di informazioni apprese con la frequenza delle lezioni di RADICALI LIBERI ED ANTIOSSIDANTI e studio autonomo di eventuali libri di riferimento in preparazione dell'esame finale o della tesi. Non devono intendersi come materiale ufficiale dell'università L'Aquila - Univaq o del prof Pitari Giusi.

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