title: Senescence-related changes in gene expression of peripheral blood mononuclear cells from octo/nonagenarians compared to their offspring.
abstract: Mechanisms determining both functional rate of decline and the time of onset in aging remain elusive. Studies of the aging process especially those involving the comparison of long-lived individuals and young controls are fairly limited. Therefore, this research aims to determine the differential gene expression profile in related individuals from villages in Pahang, Malaysia. Genome-wide microarray analysis of 18 samples of peripheral blood mononuclear cells (PBMCs) from two groups: octo/nonagenarians (80-99 years old) and their offspring (50.2 ± 4.0 years old) revealed that 477 transcripts were age-induced and 335 transcripts were age-repressed with fold changes ≥1.2 in octo/nonagenarians compared to offspring. Interestingly, changes in gene expression were associated with increased capacity for apoptosis (BAK1), cell cycle regulation (CDKN1B), metabolic process (LRPAP1), insulin action (IGF2R), and increased immune and inflammatory response (IL27RA), whereas response to stress (HSPA8), damage stimulus (XRCC6), and chromatin remodelling (TINF2) pathways were downregulated in octo/nonagenarians. These results suggested that systemic telomere maintenance, metabolism, cell signalling, and redox regulation may be important for individuals to maintain their healthy state with advancing age and that these processes play an important role in the determination of the healthy life-span.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Amirah
authors.initials: A
authors.lastname: Abdul Rahman
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Norwahidah
authors.initials: N
authors.lastname: Abdul Karim
authors.affiliation: Cyberjaya University College of Medical Sciences, 63000 Cyberjaya, Selangor, Malaysia.
authors.forename: Noor Aini
authors.initials: NA
authors.lastname: Abdul Hamid
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), UKM Hospital, Level 7, Clinical Block, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Roslan
authors.initials: R
authors.lastname: Harun
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia ; UKM Medical Molecular Biology Institute (UMBI), UKM Hospital, Level 7, Clinical Block, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
mesh_terms: D000369:Aged, 80 and over; D016922:Cellular Senescence / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results