Discover the Network Underlying the Connections Between Aging and Age-related Diseases

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 2

PMID 27582315

Citations 23

Authors

Jialiang Yang

Tao Huang

Won-Min Song

Francesca Petralia

Charles V Mobbs

Bin Zhang

Yong Zhao

Eric E Schadt

Jun Zhu

Zhidong Tu

Affiliations

Soon will be listed here.

Abstract

Although our knowledge of aging has greatly expanded in the past decades, it remains elusive why and how aging contributes to the development of age-related diseases (ARDs). In particular, a global mechanistic understanding of the connections between aging and ARDs is yet to be established. We rely on a network modelling named "GeroNet" to study the connections between aging and more than a hundred diseases. By evaluating topological connections between aging genes and disease genes in over three thousand subnetworks corresponding to various biological processes, we show that aging has stronger connections with ARD genes compared to non-ARD genes in subnetworks corresponding to "response to decreased oxygen levels", "insulin signalling pathway", "cell cycle", etc. Based on subnetwork connectivity, we can correctly "predict" if a disease is age-related and prioritize the biological processes that are involved in connecting to multiple ARDs. Using Alzheimer's disease (AD) as an example, GeroNet identifies meaningful genes that may play key roles in connecting aging and ARDs. The top modules identified by GeroNet in AD significantly overlap with modules identified from a large scale AD brain gene expression experiment, supporting that GeroNet indeed reveals the underlying biological processes involved in the disease.

Citing Articles

Impact of comorbidity on health-related quality of life in newly diagnosed patients with lymphoma or multiple myeloma: results from the PROFILES-registry.

Ekels A, van de Poll-Franse L, Issa D, Hoogendoorn M, Nijziel M, Koster A Ann Hematol. 2024; 103(12):5511-5525.

PMID: 39279019 DOI: 10.1007/s00277-024-06006-1.

An Autophagy-Associated Prognostic Gene Signature for Breast Cancer.

Cao L, Huang N, Wang J, Lan Z, Wei J, Li F Biochem Genet. 2022; 61(4):1282-1299.

PMID: 36550211 DOI: 10.1007/s10528-022-10317-1.

Exploring the Association between Glutathione Metabolism and Ferroptosis in Osteoblasts with Disuse Osteoporosis and the Key Genes Connecting them.

Wang Y, Jia Y, Xu Y, Liu X, Wang Z, Liu Y Comput Math Methods Med. 2022; 2022:4914727.

PMID: 35602340 PMC: 9119747. DOI: 10.1155/2022/4914727.

Discovery of Potential Therapeutic Drugs for COVID-19 Through Logistic Matrix Factorization With Kernel Diffusion.

Tian X, Shen L, Gao P, Huang L, Liu G, Zhou L Front Microbiol. 2022; 13:740382.

PMID: 35295301 PMC: 8919055. DOI: 10.3389/fmicb.2022.740382.

Biological mechanisms of aging predict age-related disease co-occurrence in patients.

Fraser H, Kuan V, Johnen R, Zwierzyna M, Hingorani A, Beyer A Aging Cell. 2022; 21(4):e13524.

PMID: 35259281 PMC: 9009120. DOI: 10.1111/acel.13524.

References

Blagosklonny M . Answering the ultimate question "what is the proximal cause of aging?". Aging (Albany NY). 2013; 4(12):861-77. PMC: 3615154. DOI: 10.18632/aging.100525. View

Bartke A, Chandrashekar V, Dominici F, Turyn D, Kinney B, Steger R . Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology. 2003; 4(1):1-8. DOI: 10.1023/a:1022448532248. View

Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D . Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2012; 124(3):153-64. PMC: 3466784. DOI: 10.1042/CS20120190. View

Longo V, Kennedy B . Sirtuins in aging and age-related disease. Cell. 2006; 126(2):257-68. DOI: 10.1016/j.cell.2006.07.002. View

Tacutu R, Craig T, Budovsky A, Wuttke D, Lehmann G, Taranukha D . Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing. Nucleic Acids Res. 2012; 41(Database issue):D1027-33. PMC: 3531213. DOI: 10.1093/nar/gks1155. View

Wilson W, Hay M . Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011; 11(6):393-410. DOI: 10.1038/nrc3064. View

Singhal G, Jaehne E, Corrigan F, Toben C, Baune B . Inflammasomes in neuroinflammation and changes in brain function: a focused review. Front Neurosci. 2014; 8:315. PMC: 4188030. DOI: 10.3389/fnins.2014.00315. View

Zhang B, Gaiteri C, Bodea L, Wang Z, McElwee J, Podtelezhnikov A . Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell. 2013; 153(3):707-20. PMC: 3677161. DOI: 10.1016/j.cell.2013.03.030. View

Zuo L, Motherwell M . The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease. Gene. 2013; 532(1):18-23. DOI: 10.1016/j.gene.2013.07.085. View

10.

Richardson A, Schadt E . The role of macromolecular damage in aging and age-related disease. J Gerontol A Biol Sci Med Sci. 2014; 69 Suppl 1:S28-32. DOI: 10.1093/gerona/glu056. View

11.

Zimniak P . What is the Proximal Cause of Aging?. Front Genet. 2012; 3:189. PMC: 3455862. DOI: 10.3389/fgene.2012.00189. View

12.

de la Monte S, Sohn Y, Wands J . Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease. J Neurol Sci. 1997; 152(1):73-83. DOI: 10.1016/s0022-510x(97)00131-7. View

13.

Hofree M, Shen J, Carter H, Gross A, Ideker T . Network-based stratification of tumor mutations. Nat Methods. 2013; 10(11):1108-15. PMC: 3866081. DOI: 10.1038/nmeth.2651. View

14.

Guarner V, Rubio-Ruiz M . Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol. 2014; 40:99-106. DOI: 10.1159/000364934. View

15.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

16.

Stadtman E, Oliver C, Levine R, Fucci L, Rivett A . Implication of protein oxidation in protein turnover, aging, and oxygen toxicity. Basic Life Sci. 1988; 49:331-9. DOI: 10.1007/978-1-4684-5568-7_50. View

17.

Feinberg W, Blackshear J, Laupacis A, Kronmal R, Hart R . Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995; 155(5):469-73. View

18.

Nica A, Parts L, Glass D, Nisbet J, Barrett A, Sekowska M . The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet. 2011; 7(2):e1002003. PMC: 3033383. DOI: 10.1371/journal.pgen.1002003. View

19.

Dai D, Chiao Y, Marcinek D, Szeto H, Rabinovitch P . Mitochondrial oxidative stress in aging and healthspan. Longev Healthspan. 2014; 3:6. PMC: 4013820. DOI: 10.1186/2046-2395-3-6. View

20.

von Zglinicki T, Martin-Ruiz C . Telomeres as biomarkers for ageing and age-related diseases. Curr Mol Med. 2005; 5(2):197-203. DOI: 10.2174/1566524053586545. View