Table 4.

Significant Canonical Pathways Mapped to Protein Showing Age-Dependent Quantitative Changes by IPA^*

No.	Canonical Pathway†	p	Accession‡,§	Protein Name
1	Valine, leucine, and isoleucine degradation	5.3 × 10−14	P13437 ↓	Acetyl-coenzyme A acyltransferase
			P15650	Acyl-coenzyme A dehydrogenase
			P45953	Very-long-chain acyl-coenzyme A dehydrogenase
			P17764	Acetyl-coenzyme A acetyltransferase
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional enzyme β subunit
2	Fatty acid metabolism	3.6 × 10−12	P13437 ↓	Acetyl-coenzyme A acyltransferase
			P15650	Acyl-coenzyme A dehydrogenase
			P45953	Very-long-chain acyl-coenzyme A dehydrogenase
			P17764	Acetyl-coenzyme A acetyltransferase
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional enzyme β subunit
3	Propanoate metabolism	1.7 × 10−11	P15650	Acyl-coenzyme A dehydrogenase
			P45953	Very-long-chain acyl-coenzyme A dehydrogenase
			P17764	Acetyl-coenzyme A acetyltransferase
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional enzyme β subunit
4	Pyruvate metabolism	5.2 × 10−11	P17764	Acetyl-coenzyme A acetyltransferase 1
			P08461	Dihydrolipoamide S-acetyltransferase
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
			Q6GSM4	Malate dehydrogenase 2
5	β-alanine metabolism	3.0 × 10−9	P15650	Acyl-coenzyme A dehydrogenase, long chain
			P45953	Acyl-coenzyme A dehydrogenase, very long chain
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
6	Synthesis and degradation of ketone bodies	8.2 × 10−9	P17764	Acetyl-coenzyme A acetyltransferase 1
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
7	Fatty acid elongation	2.5 × 10−8	P13437 ↓	Acetyl-coenzyme A acyltransferase 2
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
8	Citrate cycle	1.7 × 10−7	Q6DGF1	Isocitrate dehydrogenase 2 (NADP+)
			Q99NA5	Isocitrate dehydrogenase 3 (NAD+) α
			Q6GSM4	Malate dehydrogenase 2
9	Oxidative phosphorylation	1.8 × 10−8	P15999	ATP synthase, H+ transporting, mitochondrial F1 complex
			P31399 ↓	ATP synthase, H+ transporting, mitochondrial F0 complex
			Q66HF1	NADH dehydrogenase (ubiquinone) Fe-S protein 1
			P20788	Ubiquinol–cytochrome c reductase, iron-sulfur polypeptide
10	Lysine degradation	1.7 × 10−6	P17764	Acetyl-coenzyme A acetyltransferase 1
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
11	Tryptophan metabolism	1.3 × 10−5	P17764	Acetyl-coenzyme A acetyltransferase 1
			Q64428	Trifunctional protein, α subunit
			Q60587	Trifunctional protein β subunit
12	Glutathione metabolism	2.8 × 10−4	Q6DGF1	Isocitrate dehydrogenase 2 (NADP+),
			Q99NA5	Isocitrate dehydrogenase 3 (NAD+) α
13	Mitochondrial dysfunction	9.0 × 10−4	Q66HF1	NADH dehydrogenase (ubiquinone) Fe-S protein 1,
			P20788	Ubiquinol-cytochrome c reductase, iron-sulfur polypeptide 1

^*Notes: The carbonylated protein used in IPA analysis are those from Table 3.

^†The canonical pathways are in the order of significance represented by p value. In IPA, p value is a measurement of the likelihood that the pathway is associated with the data set by random chance.

^‡Swiss-Prot accession numbers are given for each protein. For those proteins without a Swiss-Prot accession number, IPI accession numbers are given instead.

^§The symbol “↓” after an accession number indicates that the protein has decreased carbonylation with aging. All other proteins showed an increase in carbonylation with age.

IPA = Ingenuity pathway analysis; NADP = nicotinamide adenine dinucleotide phosphate; NAD = nicotinamide adenine dinucleotide; ATP = adenosine-5′-triphosphate; NADH = reduced nicotinamide adenine dinucleotide.