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Aging of the immune system: cellular and molecular mechanisms

The function of the immune system in humans is severely compromised in elderly individuals leading to an increased frequency and severity of infectious diseases. In addition to this, it is associated with a low-degree inflammation, called inflammaging, which is in the background of several aging-associated phenotypic changes, e.g. frailty. During the last 5-7 years, we have characterized the aging-associated changes in the transcriptome, their functional consequences and possible regulatory factors. The focus has been in the epigenetics, i.e. mechanisms mediating the effect of environment and life-style factors on the activation of the genes. At present, the focus is on the following projects i) Viruses and immunosenescence. This far, only one virus, cytomegalovirus, is known to cause an exhaustion of the immune system. To analyze whether other viruses would have similar functions, the whole virome in the elderly individuals is characterized (using metagenomic and metatranscriptomic analyses) ii) Is there a “rejuvenating” factor in the plasma of young individuals? Already several decades ago, the parabiosis approaches in animal models suggested that this would be the case ii) Genetics of longevity. This project (as well as the epigenetic epidemiology projects) are continued by participating in international meta-analyses.

For these projects, the Vitality 90+ cohorts where biological samples are available are used. The techniques required have already been used in our previous publications.

Research funding
Pirkanmaa Hospital District
Cancer Society of Finland
The Finnish Cultural Foundation
Tampere Tuberculosis Foundation

Research group
Principal investigator
Professor Mikko Hurme,

Doctoral students
Tapio Nevalainen,
Arttu Autio,

Selected publications 2016–2019

Kananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, Kähönen M, Raitakari OT, Hervonen A, Jylhä M, Lehtimäki T, Hurme M, Jylhävä J. The trajectory of the blood DNA methylome aging rate largely  set before adulthood: evidence from two longitudinal studies. AGE 38, 65, 2016.

Kananen L, Marttila S, Nevalainen T, Jylhävä J, Mononen N, Kähönen M, Raitakari OT, Lehtimäki T, Hurme M. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns Study. BMC Genomics 17, 103, 2016.

Jylhävä J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylhä M, Hurme M. Methylomic predictors demonstrate the role of NF-kB in old-age mortality and are unrelated to the aging-associated epigenetic drift. Oncotarget 7, 19228, 2016.

Ciccarone F, Malavolta M, Calabrese R, Guastafierro T,  Bacalini NG, Reale A, Franceschi C, Capri M, Hervonen A, Hurme M, Grubeck-Loebenstein B, Koller B, Bernhardt J, Schön C, Slaagboom E, Touissant O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dolle M, Moreno-Villanueva M, Sindlinger T, Burkle A, Zampieri M, Caiafa P. Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. Aging Cell 15, 755, 2016.

Nevalainen T, Kananen L, Marttila S, Jylhävä J, Mononen N, Kähönen M, Raitakari OT, Hervonen A, Jylhä M, Lehtimäki T, Hurme M. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. Clin Epigenetics 9, 20, 2017.

Joshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Folkman Hansen T,  Gordon SD, Giulianini F, Boutin TS, Abdelaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Pina Concas M, Biino G, Tajuddin SM, Seppälä I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, Gögele M, Graff M, Hingorani A, Hottenga J, Hougaard DM, Hurme M, Ikram MA, Jylhä M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, Mägi T, Margues-Vidal P, Medland C, Milani L, Nagy R, Ollier WR, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slaagbom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen  E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtimäki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM,  van Duijn CM, Franceschini, North KE, Weir DW, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF. Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Comm  8, 610, 2017

Nevalainen T, Autio A, Mishra B, Marttila S, Jylhä M, Hurme M. Aging-associated patterns in the expression of human endogenous retroviruses. PLoS One 13, e0207407, 2018.

Fiorito G, McCrory C, Robinson O, Carmeli C, Ochoa Rosales, C, Zhang Y, Colicino E, Dugue PA, Artaud F, McKay GJ, Jeong A, Mishra PP, Nost TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini S, the BIOS Consortium, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA, Young I, McKnight AJ, Lund E, Baccarelli A, Milne R, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtimäki T, Elliot P, Stringhini S, Vineis P, Polodoro S, the Lifepath consortium. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis. Aging in press.

Mandaviya PR, Joehanes R, Brody J, Castillo-Fernandez JE, Dekkers KKF, Do AN, Graff M, Hänninen IK, Tanaka T, de Jonge EAL, Kiefte-de Jong JC, Anbsher DM, Aslibekyan S, de Rijke YB, Fornage M, Herbandez DG, Hurme MA, Ikram MA, Jacques PF, Justice AE, Kiel DP, Lemaitre RN, Mendelson MM, Mikkilä V, Moore AZ, Pallister T, Raitakari OT, Schalkwijk CG, Sha J, Slagboom EP, Smith CE, Stehower CDA, Tsai PC, Uitterlinden AG, van der Kallen CJH, van Heemst DD, BIOS consortium, CHARGE consortium, Arnett DK, Bandinelli S, Bell JT, Heijmans BBT, Lehtimäki T, Levy D, North KE, Sotoodehnia N, van Greevenbroek MMJ, van Meurs JBJ, Heil SG. Association of dietary folate and vitamin B12 intake with genome-wide DNA methylation in blood: a large scale epigenome-wide analysis of 5,841 individuals. Am J Clin Nutr in press

Meryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylhävä J, Hurme M, Trieb K, Grubeck-Loebenstein B. Fcm receptor as a new costimulatory molecule for T cells. Cell Rep in press

Professor Marja Jylhä
Professor Terho Lehtimäki

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