Specific Differentially Methylated and Expressed Genes in People with Longevity Family History
Abstract
Background: We attempt to identify specific differentially methylated and expressed genes in people with longevity family history, it will contribute to discover significant features about human longevity.
Methods: A prevalence study was conducted during October 2017 to January 2019 in Bama County of Guangxi, China and individuals were recruited and grouped into longevity family (n=60) and non-longevity family (n=60) to identify differentially methylated genes (DMGs). The expression profile dataset GSE16717 was downloaded from the GEO database in which individuals were divided into 3 groups, namely longevity (n=50), longevity offspring (n=50) and control (n=50) for identifying differentially expressed genes (DEGs). It was considered significantly different when P or adjusted P£0.05.
Results: In total, 117 longevity-related hypermethylated genes enriched in interleukin secretion/production regulation, chemokine signaling pathway and natural killer cell-mediated cytotoxicity. Another 296 significant key longevity-related DEGs primarily involved in protein binding, nucleus, cytoplasm, T cell receptor signaling pathway and Metabolic pathway, H19 and PFKFB4 were found to be both methylated and downregulated in people with longevity family history.
Conclusion: Human longevity-specific genes involve in many immunity regulations and cellular immunity pathways, H19 and PFKFB4 show hypermethylated and suppressed status in people with longevity family history and might serve as longevity candidate genes.
1. Armstrong NJ, Mather KA, Thalamuthu A, et al (2017). Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks. Epigenomics, 9(5):689-700.
2. Barcellos LF, Klitz W, Field LL, et al (1997). Association mapping of disease loci, by use of a pooled DNA genomic screen. Am J Hum Genet, 61(3): 734–747.
3. Bell JT, Pai AA, Pickrell JK, et al (2011). DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol, 12(1):R10.
4. Britanova OV, Putintseva EV, Shugay M, et al (2014). Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling. J Immunol, 192(6):2689-98.
5. Bucci L, Ostan R, Giampieri E, et al (2014). Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status. Exp Gerontol, 54:14-20.
6. Cardoso CAM, Guidugli-Lazzarini KR, Hartfelder K (2018). DNA methylation affects the lifespan of honey bee (Apis mellifera L.) workers - Evidence for a regulatory module that involves vitellogenin expression but is independent of juvenile hormone function. Insect Biochem Mol Biol, 92:21-29.
7. Chesney J, Clark J, Lanceta L, Trent JO, Telang S (2015). Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor. Oncotarget, 6(20):18001-11.
8. Christiansen J, Kolte AM, Hansen TVO, Nielsen FC (2009). IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J Mol Endocrinol, 43(5):187-195.
9. de Toda IM, Mate I, Vida C, et al (2016). Immune function parameters as markers of biological age and predictors of longevity. Aging (Albany NY), 8(11):3110-3119.
10. Derhovanessian E, Maier AB, Beck R, et al (2010). Hallmark Features of Immunosenescence Are Absent in Familial Longevity. J Immunol, 185(8):4618-24.
11. Feil R, Fraga MF (2012). Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet, 13(2):97-109.
12. Fiorito G, Polidoro S, Dugue PA, et al (2017). Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation. Sci Rep, 7(1):16266.
13. Hannum G, Guinney J, Zhao L, et al (2013). Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell, 49(2):359-367.
14. Heijmans BT, Kremer D, Tobi EW, et al (2007). Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus. Hum Mol Genet, 16(5):547-54.
15. Horvath S, Pirazzini C, Bacalini MG, et al (2015). Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY), 7(12):1159-70.
16. Huang DW, Sherman BT, Lempicki RA (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 4(1):44-57.
17. Iempridee T (2017). Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines. Exp Biol Med (Maywood), 242(2):184-193.
18. Jasiulionis MG (2018). Abnormal Epigenetic Regulation of Immune System during Aging. Front Immunol, 9:197.
19. Kogelman LJA, Kadarmideen HN (2014). Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data. BMC Syst Biol, 8:S5.
20. Langfelder P, Horvath S (2008). WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics, 9:559.
21. Li S, Wong EM, Bui M, et al (2018). Causal effect of smoking on DNA methylation in peripheral blood: a twin and family study. Clin Epigenetics, 10:18.
22. Li Y, Huang Y, Liang X, et al (2017). Apolipoprotein C-I Polymorphism and Its Association with Serum Lipid Levels and Longevity in the Bama Population. Int J Environ Res Public Health, 14(5):505.
23. Lin Q, Weidner CI, Costa IG, et al (2016). DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging (Albany NY), 8(2):394-401.
24. Liu X, Liu C, Shan K, et al (2018). Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function. Cell Physiol Biochem, 50(1):246-260.
25. Matouk I, Raveh E, Ohana P, et al (2013). The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci, 14(2):4298-316.
26. McEwen LM, Morin AM, Edgar RD, et al (2017). Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region. Epigenetics Chromatin, 10:21.
27. Mendelsohn AR, Larrick JW (2017). Epigenetic Drift Is a Determinant of Mammalian Lifespan. Rejuvenation Res, 20(5):430-436.
28. Minchenko OH, Ochiai A, Opentanova IL, et al (2005). Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors. Biochimie, 87(11):1005-10.
29. Passtoors WM, Boer JM, Goeman JJ, et al (2012). Transcriptional Profiling of Human Familial Longevity Indicates a Role for ASF1A and IL7R. PLoS One, 7(1):e27759.
30. Sasaki N, Toyoda M, Yoshimura H, et al (2018). H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells. Oncotarget, 9(78): 34719–34734.
31. Seim I, Ma S, Gladyshev VN (2016). Gene expression signatures of human cell and tissue longevity. NPJ Aging Mech Dis, 2:16014.
32. Vaiserman AM, Koliada AK, Jirtle RL (2017). Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species. Epigenetics Chromatin, 10(1):38.
33. Vander Heiden MG, Cantley LC, Thompson CB (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930):1029-33.
34. Xiao FH, He YH, Li QG, et al (2015). A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes. PLoS One, 10(3):e0120388.
35. Xiao FH, Kong QP, Perry B, He YH (2016). Progress on the role of DNA methylation in aging and longevity. Brief Funct Genomics, 15(6):454-459.
36. Yerges-Armstrong LM, Chai S, O'Connell JR, et al (2016). Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene. J Gerontol A Biol Sci Med Sci, 71(10):1295-9.
37. Zhang Y, Hapala J, Brenner H, Wagner W (2017). Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging. Clin Epigenetics, 9: 9.
38. Zhang Z, Gao W, Long QQ, et al (2017). Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Scientific Reports, 7:7491.
2. Barcellos LF, Klitz W, Field LL, et al (1997). Association mapping of disease loci, by use of a pooled DNA genomic screen. Am J Hum Genet, 61(3): 734–747.
3. Bell JT, Pai AA, Pickrell JK, et al (2011). DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol, 12(1):R10.
4. Britanova OV, Putintseva EV, Shugay M, et al (2014). Age-Related Decrease in TCR Repertoire Diversity Measured with Deep and Normalized Sequence Profiling. J Immunol, 192(6):2689-98.
5. Bucci L, Ostan R, Giampieri E, et al (2014). Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status. Exp Gerontol, 54:14-20.
6. Cardoso CAM, Guidugli-Lazzarini KR, Hartfelder K (2018). DNA methylation affects the lifespan of honey bee (Apis mellifera L.) workers - Evidence for a regulatory module that involves vitellogenin expression but is independent of juvenile hormone function. Insect Biochem Mol Biol, 92:21-29.
7. Chesney J, Clark J, Lanceta L, Trent JO, Telang S (2015). Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor. Oncotarget, 6(20):18001-11.
8. Christiansen J, Kolte AM, Hansen TVO, Nielsen FC (2009). IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J Mol Endocrinol, 43(5):187-195.
9. de Toda IM, Mate I, Vida C, et al (2016). Immune function parameters as markers of biological age and predictors of longevity. Aging (Albany NY), 8(11):3110-3119.
10. Derhovanessian E, Maier AB, Beck R, et al (2010). Hallmark Features of Immunosenescence Are Absent in Familial Longevity. J Immunol, 185(8):4618-24.
11. Feil R, Fraga MF (2012). Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet, 13(2):97-109.
12. Fiorito G, Polidoro S, Dugue PA, et al (2017). Social adversity and epigenetic aging: a multi-cohort study on socioeconomic differences in peripheral blood DNA methylation. Sci Rep, 7(1):16266.
13. Hannum G, Guinney J, Zhao L, et al (2013). Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell, 49(2):359-367.
14. Heijmans BT, Kremer D, Tobi EW, et al (2007). Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus. Hum Mol Genet, 16(5):547-54.
15. Horvath S, Pirazzini C, Bacalini MG, et al (2015). Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY), 7(12):1159-70.
16. Huang DW, Sherman BT, Lempicki RA (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 4(1):44-57.
17. Iempridee T (2017). Long non-coding RNA H19 enhances cell proliferation and anchorage-independent growth of cervical cancer cell lines. Exp Biol Med (Maywood), 242(2):184-193.
18. Jasiulionis MG (2018). Abnormal Epigenetic Regulation of Immune System during Aging. Front Immunol, 9:197.
19. Kogelman LJA, Kadarmideen HN (2014). Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data. BMC Syst Biol, 8:S5.
20. Langfelder P, Horvath S (2008). WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics, 9:559.
21. Li S, Wong EM, Bui M, et al (2018). Causal effect of smoking on DNA methylation in peripheral blood: a twin and family study. Clin Epigenetics, 10:18.
22. Li Y, Huang Y, Liang X, et al (2017). Apolipoprotein C-I Polymorphism and Its Association with Serum Lipid Levels and Longevity in the Bama Population. Int J Environ Res Public Health, 14(5):505.
23. Lin Q, Weidner CI, Costa IG, et al (2016). DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging (Albany NY), 8(2):394-401.
24. Liu X, Liu C, Shan K, et al (2018). Long Non-Coding RNA H19 Regulates Human Lens Epithelial Cells Function. Cell Physiol Biochem, 50(1):246-260.
25. Matouk I, Raveh E, Ohana P, et al (2013). The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci, 14(2):4298-316.
26. McEwen LM, Morin AM, Edgar RD, et al (2017). Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region. Epigenetics Chromatin, 10:21.
27. Mendelsohn AR, Larrick JW (2017). Epigenetic Drift Is a Determinant of Mammalian Lifespan. Rejuvenation Res, 20(5):430-436.
28. Minchenko OH, Ochiai A, Opentanova IL, et al (2005). Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors. Biochimie, 87(11):1005-10.
29. Passtoors WM, Boer JM, Goeman JJ, et al (2012). Transcriptional Profiling of Human Familial Longevity Indicates a Role for ASF1A and IL7R. PLoS One, 7(1):e27759.
30. Sasaki N, Toyoda M, Yoshimura H, et al (2018). H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells. Oncotarget, 9(78): 34719–34734.
31. Seim I, Ma S, Gladyshev VN (2016). Gene expression signatures of human cell and tissue longevity. NPJ Aging Mech Dis, 2:16014.
32. Vaiserman AM, Koliada AK, Jirtle RL (2017). Non-genomic transmission of longevity between generations: potential mechanisms and evidence across species. Epigenetics Chromatin, 10(1):38.
33. Vander Heiden MG, Cantley LC, Thompson CB (2009). Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324(5930):1029-33.
34. Xiao FH, He YH, Li QG, et al (2015). A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes. PLoS One, 10(3):e0120388.
35. Xiao FH, Kong QP, Perry B, He YH (2016). Progress on the role of DNA methylation in aging and longevity. Brief Funct Genomics, 15(6):454-459.
36. Yerges-Armstrong LM, Chai S, O'Connell JR, et al (2016). Gene Expression Differences Between Offspring of Long-Lived Individuals and Controls in Candidate Longevity Regions: Evidence for PAPSS2 as a Longevity Gene. J Gerontol A Biol Sci Med Sci, 71(10):1295-9.
37. Zhang Y, Hapala J, Brenner H, Wagner W (2017). Individual CpG sites that are associated with age and life expectancy become hypomethylated upon aging. Clin Epigenetics, 9: 9.
38. Zhang Z, Gao W, Long QQ, et al (2017). Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Scientific Reports, 7:7491.
| Files | ||
| Issue | Vol 50 No 1 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v50i1.5082 | |
| Keywords | ||
| Differentially methylated genes Differentially expressed genes People Longevity family history | ||
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How to Cite
1.
LI C, NONG Q, GUAN B, HE H, ZHANG Z. Specific Differentially Methylated and Expressed Genes in People with Longevity Family History. Iran J Public Health. 2020;50(1):152-160.
