Aging of the immune system: cellular and molecular mechanisms / Mikko Hurme

Aging is associated with a functional decline of the immune system, which manifests as an increased morbidity and mortality to infectious diseases and cancer. We focus on the analysis of the function and distribution of the cells of human immune system in aged individuals. Using genome-wide gene expression analysis we are able to find those genes the expression of which is responsible for the observed functional changes. Additionally, the epigenetic mechanisms (e.g. DNA methylation) explaining the effects of environmental and life-style factors on the gene expression profile are analyzed. These observations are correlated to the biological and phenotypic  markers. We also focus on characterization of novel biomarkers, which would be informative on the function of the immune system and, more generally, on the biological aging process. The biological samples are from the ongoing Vitality 90+ study, as well as from the EU consortium MARK-AGE.

Funding
The Academy of Finland
European  Union (7th FP Biomarkers of Human Aging, MARK-AGE)
Pirkanmaa Hospital District

Research group
Principal investigator
Professor Mikko Hurme, mikko.a.hurme[at]uta.fi, Medical School, University of Tampere

Post Doc researcher
Juulia Jylhävä, juulia.jylhava[at]uta.fi. Genomics and biomarkers of aging

Doctoral students
Saara Marttila, saara.marttila[at]uta.fi. Ageing-associated epigenetic changes and transgenerational inheritance
Laura Kanenen, Laura.Kananen[at]uta.fi. Ageing-associated changes in transcription and epigenetics
Tapio Nevalainen, tapio.l.nevalainen[at]uta.fi. Ageing-associated epigenetic changes

Selected publications

Kananen L, Nevalainen T, Jylhävä J, Marttila S, Hervonen A, Jylhä M, Hurme M.  Cytomegalovirus infection accelerates epigenetic aging. Exp Gerontol. 2015 Dec;72:227-9. doi: 10.1016/j.exger.2015.10.008. Epub 2015 Oct 17. PubMed PMID: 26485162.

Nevalainen T, Kananen L, Marttila S, Jylhä M, Hervonen A, Hurme M, Jylhävä J.  Transcriptomic and epigenetic analyses reveal a gender difference in aging-associated inflammation: the Vitality 90+ study. Age (Dordr). 2015 Aug;37(4):9814. doi: 10.1007/s11357-015-9814-9. Epub 2015 Jul 19. PubMed PMID: 26188803; PubMed Central PMCID: PMC4506741.

Marttila S, Kananen L, Jylhävä J, Nevalainen T, Hervonen A, Jylhä M, Hurme M.  Length of paternal lifespan is manifested in the DNA methylome of their nonagenarian progeny. Oncotarget. 2015 Oct 13;6(31):30557-67. doi: 10.18632/oncotarget.5905. PubMed PMID: 26436701.

Marttila S, Kananen L, Häyrynen S, Jylhävä J, Nevalainen T, Hervonen A, Jylhä  M, Nykter M, Hurme M. Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression. BMC Genomics. 2015 Mar 14;16:179. doi: 10.1186/s12864-015-1381-z. PubMed PMID: 25888029; PubMed Central  PMCID: PMC4404609.

Marttila S, Nevalainen T, Kananen L, Jylhävä J, Jylhä M, Hervonen A, Ilonen J, Hurme M. Number of sons contributes to ageing-associated inflammation. Sci Rep. 2015 Feb 27;5:8631. doi: 10.1038/srep08631. PubMed PMID: 25721217; PubMed Central PMCID: PMC4342565.

Jylhävä J, Raitanen J, Marttila S, Hervonen A, Jylhä M, Hurme M. Identification of a prognostic signature for old-age mortality by integrating genome-wide transcriptomic data with the conventional predictors: the Vitality 90+ Study. BMC Med Genomics. 2014 Sep 11;7:54. doi: 10.1186/1755-8794-7-54. PubMed PMID: 25213707; PubMed Central PMCID: PMC4167306.

Marttila S, Jylhävä J, Nevalainen T, Nykter M, Jylhä M, Hervonen A, Tserel L, Peterson P, Hurme M. Transcriptional analysis reveals gender-specific changes in  the aging of the human immune system. PLoS One. 2013 Jun 11;8(6):e66229. doi: 10.1371/journal.pone.0066229. Print 2013. PubMed PMID: 23776639; PubMed Central PMCID: PMC3679079.

Jylhävä J, Nevalainen T, Marttila S, Jylhä M, Hervonen A, Hurme M. Characterization of the role of distinct plasma cell-free DNA species in age-associated inflammation and frailty. Aging Cell. 2013 Jun;12(3):388-97. doi:  10.1111/acel.12058. Epub 2013 Apr 1. PubMed PMID: 23438186.

J Jylhävä, C Eklund, M Jylhä, A Hervonen, M Hurme. Expression profiling of immune-associated genes in peripheral blood mononuclear cells reveals baseline differences in costimulatory signalling between nonagenarians and younger controls. Biogerontology 11, 671, 2010.

J Jylhävä, T Kotipelto, A Raitala, M Jylhä, A Hervonen, M Hurme. Aging is associated with quantitative and qualitative changes in circulating cell-free DNA: the Vitality 90+ Study. Mech Ageing Dev 132, 20, 2011.

S Marttila, J Jylhävä, M Pesu, S Hämäläinen, M Jylhä, A Hervonen, M Hurme. IL-7 concentration is increased in nonagenarians but is not associated with markers of T cell immunosenescence. Exp Gerontol 46, 1000, 2011.

Collaborators
University of Tampere, School of Health Sciences (Professors Antti Hervonen and Marja Jylhä)