Gene Expression Profile in Different Age Groups and Its Association with Cognitive Function in Healthy Malay Adults in Malaysia

Abstract

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.

Metabolomics Profiling of Age-Associated Metabolites in Malay Population

“…In addition, 9(E),11(E)-conjugated linoleic acid, a form of ω -6 fatty acid, was inversely associated with age in Malay males. Interestingly, our previous transcriptomics study shows that endogenous synthesis of ω -3 and ω -6 fatty acids is impaired in the older Malays due to downregulation of FADS genes that are involved in the conversion of dietary α -linolenic acid and linoleic acid to ω -3 and ω -6 fatty acids, respectively, supporting the recommendation of long-chain fatty acid supplementation based on FADS gene expressions [ 21 ].…”

“…Our previous transcriptomics and proteomics studies show that several expressions of genes and proteins related to cholesterol metabolism are altered with age in Malays. These include age-associated increased expression of the TM7SF2 gene, which is involved in cholesterol biosynthesis, and decreased ALOX5 expression, a gene taking part in leukotriene production [ 21 ]. At the protein level, lipoprotein AOPA4 is higher in Malays beyond 60 years, while lipoprotein (a) decreases with age [ 22 ].…”

“…Our previous study shows that increased oxidative stress is associated with advanced age in Malays, such that DNA damage and protein carbonyl are predictors for cognitive impairment in the population [ 20 ]. Further study on the transcriptome of peripheral blood mononuclear cells (PBMCs) indicates that gene expressions related to inflammation, signal transduction, metabolic, and nociception pathways are altered with age in the Malays [ 21 ]. Our proteomics profiling of plasma from the Malays reports that the age-associated protein changes are related to the cholesterol metabolic process, fatty acid biosynthetic process, and response to toxic substances [ 22 ].…”