title: Identification of the dichotomous role of age-related LCK in calorie restriction revealed by integrative analysis of cDNA microarray and interactome.
abstract: Among the many experimental paradigms used for the investigation of aging, the calorie restriction (CR) model has been proven to be the most useful in gerontological research. Exploration of the mechanisms underlying CR has produced a wealth of data. To identify key molecules controlled by aging and CR, we integrated data from 84 mouse and rat cDNA microarrays with a protein-protein interaction network. On the basis of this integrative analysis, we selected three genes that are upregulated in aging but downregulated by CR and two genes that are downregulated in aging but upregulated by CR. One of these key molecules is lymphocyte-specific protein tyrosine kinase (LCK). To further confirm this result on LCK, we performed a series of experiments in vitro and in vivo using kidneys obtained from aged ad libitum-fed and CR rats. Our major significant findings are as follows: (1) identification of LCK as a key molecule using integrative analysis; (2) confirmation that the age-related increase in LCK was modulated by CR and that protein tyrosine kinase activity was decreased using a LCK-specific inhibitor; and (3) upregulation of LCK leads to NF-κB activation in a ONOO(-) generation-dependent manner, which is modulated by CR. These results indicate that LCK could be considered a target attenuated by the anti-aging effects of CR. Integrative analysis of cDNA microarray and interactome data are powerful tools for identifying target molecules that are involved in the aging process and modulated by CR.
authors: Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, 609-735, Republic of Korea.
authors: Daeui
authors: D
authors: Park
authors: Eun Kyeong
authors: EK
authors: Lee
authors: Eun Jee
authors: EJ
authors: Jang
authors: Hyoung Oh
authors: HO
authors: Jeong
authors: Byoung-Chul
authors: BC
authors: Kim
authors: Young Mi
authors: YM
authors: Ha
authors: Seong Eui
authors: SE
authors: Hong
authors: Byung Pal
authors: BP
authors: Yu
authors: Hae Young
authors: HY
authors: Chung
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D002149:Energy Intake / Q000235:genetics*; D005786:Gene Expression Regulation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018384:Oxidative Stress / Q000235:genetics; D012313:RNA / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D012313:RNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)