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Factsheet by Kaare Christensen

Group name: The Danish Aging Research
Center Group leader: Kaare Christensen
Group members: Kaare Christensen, Professor; Bernard Jeune, Associate professor; Axel Skytthe, Senior data analyst; Lene Christian-sen, Professor; James W. Vaupel, Profes-sor; Matt McGue, Professor; Karen Ander-sen-Ranberg, Professor; Mikael Thinggaard, Assistant professor; Marianne Nygaard, Assistant professor; Signe Høi Rasmussen, Ph.D. student
Department & University/Hospital/Other:
Department of Public Health, University of Southern Denmark, Odense, Denmark
Funding sources:
Danish National Research Foundation; U.S. National Institute on Aging - National Institutes of Health [Grant PO1-AG08761]; Danish Health Insurance Foundation [Grant 2006B139]; Danish Agency for Science, Technology and Innovation; Danish Interdisciplinary Research Council; The Danish Council for Independent ResearchǀMedical Sciences [Grant 09-070081 and 6110-00016]; The Lundbeck Foundation [R83-A8168]; The Novo Nordisk Foundation; The Clinical Insti-tute of Research, University of Southern Denmark; The Health Foundation (Helsefonden) [Grant nr.16-B-0271]; U.S. National Institutes of Health [Grant UO1-AG023712]; U.S. National Institutes of Health [Grant PO1-AG031719]. The Danish Aging Research Center is supported by a grant from the Velux Foundation.

Description of research (please divide into main projects):
Background
There is a growing concern that the improved survival among elderly people will increase the pro-portion of oldest old with physical and cognitive impairments.

Overall aim for the previous and the ongoing studies
To determine the health and cognitive and physical function of the population of long-lived individ-uals, and to investigate whether these improve, decrease or are stable over cohorts. And, moreover, to identify genetic and environmental determinants of exceptional functioning at the highest ages.

Secular trends in the health and functioning of the very old
Following the Danish 1905 Cohort from age 93 to 100 years, we found that the age trajectory of av-erage cognitive and physical functioning is constant at the population level in this age range because of higher mortality among those with the lowest cognitive scores. This suggests that exceptional lon-gevity is not associated with higher levels of cognitive impairment.
We also found that 95-year olds born in 1915 performed better both in the cognitive tests and in the activities of daily living score compared to 93-year olds born in 1905. This indicates that more peo-ple are living to older ages with better overall functioning. We are currently investigating whether this improvement is also present among centenarians born 20 years apart.

Genetic studies of aging and cognitive function
Twin and family studies indicate a moderate to substantial influence of genetic factors on survival probability and cognitive decline during aging. Our previous and ongoing genetic studies focus on investigating both common and rare variants in candidate genes (e.g. Apo-E), and we carry out ge-nome-wide studies of common genetic variants and their influence on these age-related traits. Cur-rent studies also include epigenetic and gene expression studies.

Key publications (last 10 years):
Rasmussen, S. H., Andersen-Ranberg, K., Thinggaard, M., Jeune, B., Skytthe, A., Christiansen, L., ... & Christensen, K. (2017). Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies-secular trends in the health and functioning of the very old. International journal of epide-miology.
Petersen, I., McGue, M., Tan, Q., Christensen, K., & Christiansen, L. (2016). Change in depression symptomatology and cognitive function in twins: a 10-year follow-up study. Twin Research and Human Genetics, 19(02), 104-111.

Mengel-From, J., Soerensen, M., Nygaard, M., McGue, M., Christensen, K., & Christiansen, L. (2016). Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71(9), 1151-1159.

Christensen, K., Thinggaard, M., Oksuzyan, A., Steenstrup, T., Andersen-Ranberg, K., Jeune, B., ... & Vaupel, J. W. (2013). Physical and cognitive functioning of people older than 90 years: a compar-ison of two Danish cohorts born 10 years apart. The Lancet, 382(9903), 1507-1513.

Lindahl-Jacobsen, R., Tan, Q., Mengel-From, J., Christensen, K., Nebel, A., & Christiansen, L. (2013). Effects of the APOE ε2 allele on mortality and cognitive function in the oldest old. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 68(4), 389-394.

Christensen, K., McGue, M., Petersen, I., Jeune, B., & Vaupel, J. W. (2008). Exceptional longevity does not result in excessive levels of disability. Proceedings of the National Academy of Sciences, 105(36), 13274-13279.

Engberg, H., Christensen, K., Andersen-Ranberg, K., & Jeune, B. (2008). Cohort changes in cogni-tive function among Danish centenarians. Dementia and geriatric cognitive disorders, 26(2), 153-160.

Iachine, I., Skytthe, A., Vaupel, J. W., McGue, M., Koskenvuo, M., Kaprio, J., ... & Christensen, K. (2006). Genetic influence on human lifespan and longevity. Human genetics, 119(3), 312-321.
McGue, M., & Christensen, K. (2002). The heritability of level and rate-of-change in cognitive func-tioning in Danish twins aged 70 years and older. Experimental aging research, 28(4), 435-451.

Key collaborations:
Danish: Univeristy of Copenhagen, Aarhus University and Odense University Hospital, Odense.
International: Max-Planck Institute for Demographic Research, Rostock, Germany
Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA

Infrastructure:
The group includes participants with expertise in epidemiology, genetics, statistics, and bioinformat-ics.
Technical resources include:
• Hand Dynamometer: Equipment to measure hand grip strenght
• Peak flow meter and Spirometer: Equipment to measure lung function
• Electrocardiograph: Equipment to obtain an electrocardiogram (ECG)
• Within our domestic laboratory facilities at department of Clinical Genetics, Odense Univer-sity Hospital, we have access to the equipment and expertise necessary for carrying out me-dium and high-through-put genetic variation and gene expression studies.

Last Updated 16.03.2021