The Human Life Cycle—Biological, Social, and Cultural Aspects
The human life cycle has been undergoing fundamental changes since the 20th century. Biological, technological, social, and cultural factors interact in this process, making collaboration among various scientific disciplines necessary to address the pressing problems that arise as a result.
There are significant cultural differences in the cognitive modeling of these findings, some of which are only established through performance: What is youth? What is old age?
The 3rd subprogram investigated the biological, social, and cultural aspects of the human life cycle and was successfully completed in 2012.
The joint closing conference "The Human Life Cycle—Biological, Social, and Cultural Aspects" (PDF) took place on June 14–15, 2012, in Heidelberg.
Sponsored by
Changes in Memory Function in the Aging Brain—Functional, Biochemical, and Genetic Aspects
As part of the project’s multimodal approach, significant findings were obtained regarding the biopsychological correlates of age-related changes in memory performance, which contribute to the current state of research in this field. The functional results and their mathematical modeling, as well as the spectroscopic analyses, support hypotheses regarding a neural interplay between degradation (dedifferentiation) and adaptation (compensation) processes as people age. Structurally, the level of physical/athletic activity appears to significantly influence the integrity of the hippocampus in particular, as a key memory structure. With regard to genetic factors, analysis of the SCN1A gene variant rs10930201 revealed, in addition to age-independent structural findings (reduction in gray matter in frontal regions, including the insula), clear age-associated effects at both the functional and metabolic levels. In particular, it was found that carriers of the vulnerability allele exhibit poorer working memory performance, which is associated with increased frontal and cingulate activation. At the same time, the age-related increase in mI was significantly higher in carriers of the vulnerability allele.
Publications resulting from the project:
- Tunc-Skarka N., Meier S., Demirakca T., Sack M., Weber-Fahr W., Brusniak W., Wolf I., Matthäus F., Schulze T.G., Diener C., Ende G. (2014). Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol. NMR Biomed. 27(2): 228–234.
- Matthäus F., Schmidt J.P., Banerjee A., Schulze T.G., Demirakca T., Diener, C. (2012). Effects of age on the structure of functional connectivity networks during episodic and working memory tasks. Brain Connectivity 2: 113–124.
- Meier S., Demirakca T., Brusniak W., Wolf I., Liebsch K., Tunc-Skarka N., Nieratschker V., Witt S.H., Schmäl C., Matthäus F., Ende G., Flor H., Rietschel M., Diener C., Schulze T.G. (2012). SCN1A affects brain structure and the neural activity of the aging brain. Biological Psychiatry 72: 677–683.
- Matthäus F., Schmidt J.P., Demirakca T., Diener C. (2011). Structural analysis of functional connectivity related to memory reveals network changes in memory function over the life span. 20th Annual Computational Neuroscience Meeting: CNS, Stockholm, Sweden. BMC Neuroscience 12 (Suppl 1): 71.
Research Fellows:
- Dr. Carsten Diener
- Dr. Franziska Matthäus
Associate project partners
- PD Dr. Gabriela Ende
- Prof. Dr. Thomas G. Schulze
A person is as old as their stem cells
Adult (or somatic) stem cells ensure the regeneration of corresponding tissues throughout a person’s lifetime, which is why these endogenous stem cells, in particular, are responsible for the aging of the entire organism. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are two types of multipotent stem cells, with HSCs in particular also being successfully used in clinical applications. The goal of the project was to investigate age-related changes in HSCs and MSCs and to model them using mathematical models. The central hypothesis was that epigenetic programming significantly determines these aging processes. The interdisciplinary collaboration between clinical departments, a natural science research institute, and the Institute for Applied Mathematics enabled the integration of medical, biological, and mathematical aspects for a comprehensive investigation from various perspectives. The study was based on the assumption that the biological mechanisms of the human life cycle are based less on the random accumulation of errors in cellular metabolism and more on a purposeful and predetermined “aging program” encoded in our stem cells. The results of the study revealed a correlation between replicative senescence and a continuous change in their stem cell potential as well as in their mRNA and miRNA expression profiles. Stem cells from people of different ages exhibited differences in methylation and gene expression. Using the developed mathematical models, it was shown that lifelong hematopoiesis is compatible with a limit of 50 cell divisions, as well as possible changes in the ratio of stem cells to progenitor cells.
Publications resulting from the project:
- Cholewa D., Stiehl T., Schellenberg A., Bokermann G., Joussen S., Koch C., Walenda T., Pallua N., Marciniak-Czochra A., Suschek C.V., Wagner W. (2011). Expansion of adipose mesenchymal stromal cells is affected by human platelet lysate and plating density. Cell Transplant 20(9): 1409–1422.
- Bork S., Horn P., Castoldi M. (2010). Adipogenic differentiation of human mesenchymal stromal cells is downregulated by microRNA-369-5p and upregulated by microRNA-371. J. Cell Physiol. Dec. 6.
- Bork S., Pfister S., Witt H., Horn P., Korn B., Ho A.D., and Wagner W. (2010). Changes in DNA Methylation Patterns upon Long-Term Culture and Aging of Human Mesenchymal Stromal Cells. Aging Cell 9: 54–63.
- Marciniak-Czochra A. (2009). Mathematical Models of Stem Cell Renewal and Differentiation. Oberwolfach Reports 2.
- Marciniak-Czochra A., Stiehl T., Wagner W. (2009). Modeling of Replicative Senescence in Hematopoietic Development. AGING 1: 723–732.
- Wagner W., Bork S., Horn P. (2009). Aging and replicative senescence have related effects on human stem and progenitor cells. PLoS ONE 4: e5846.
- Horn P., Bork S., Diehlmann A., Walenda T., Eckstein V., Ho A.D., Wagner W. (2008). Isolation of human mesenchymal stromal cells is more efficient by red blood cell lysis. Cytotherapy 10: 676–685.
- Marciniak-Czochra A., Stiehl T., Ho A.D., Jaeger W., and Wagner W. (2008). Modeling asymmetric cell division in hematopoietic stem cells—regulation of self-renewal is essential for efficient repopulation. Stem Cells Dev. 17: 1–10.
- Wagner W., Horn P., Bork S., Ho A.D. (2008). Aging of hematopoietic stem cells is regulated by the stem cell niche. Exp. Gerontol. 43: 974–980.
- Wagner W., Horn P., Castoldi M., Diehlmann A., Bork S., Saffrich R., Benes V., Blake J., Pfister S., Eckstein V., Ho A.D. (2008). Replicative Senescence of Mesenchymal Stem Cells – a Continuous and Organized Process. PLoS ONE 3(5): e2213.
Research Fellows:
- Dr. Simone Bork
- Dr. Anna Marciniak-Czochra
- PD Dr. Stefan Pfister
Associated Project Partner:
Prof. Dr. Dr. Wolfgang Wagner
Religious and Poetic Constructions of Age. Conceptualization and Interpretation of Age Milestones in the Life Cycle
The high variability of aging in humans also influences the cultural understanding of aging processes and life stages. The current demographic shift was set in motion by a steady increase in life expectancy over the past 150 years. On the one hand, the extended life cycle seems to make the connection between reproduction, senescence, and mortality—as initially assumed by evolutionary biology—increasingly questionable; on the other hand, however, cognitive conceptions of the life cycle have changed relatively little. Thus, biomedical evidence and sociocultural concepts have increasingly come into dissonance with one another, as the debate over the retirement age exemplifies. To explain why, despite significantly longer life expectancy in the modern era, traditional, pre-modern, and early-modern concepts of the human life cycle continue to influence our thinking to this day, it is necessary to describe the various conceptions of the stages of life from a long historical perspective. Subsequently, the study examined the rules according to which these concepts were cognitively modeled in each case and how they relate to one another to this day. The period under investigation spanned from the time of the Old Testament to more recent literature from around 1950 and was divided into four time periods corresponding to the four disciplines involved. The study focused on the question of how, since antiquity, the sometimes topical descriptive patterns in religious and poetic texts opened up cultural scope for interpreting the human life course, and how this allowed a shift in discourses on age to take shape, which, on the one hand, drew on traditional conceptual frameworks but, at the same time, was able to transcend and renew them through contextual and performative variation.
Publications resulting from the project:
- Elm, Dorothee/Fitzon, Thorsten/Liess, Kathrin (2012): From Wise Old Age to Lived Old Age. Variations on a Topos. In: Heinz Häfner and Peter Graf Kielmansegg (eds.): Age and Aging. Realities and Interpretations. Berlin/Heidelberg, 73–90.
- Fitzon, Thorsten/Elm, Dorothee/Liess, Kathrin/Linden, Sandra (eds.) (2011): Age Cutoffs: Time and Age. In: Literature, Theology, and History. Berlin/New York.
- Fitzon, Thorsten/Linden, Sandra/Liess, Kathrin/Elm, Dorothee (2011): Textual Perspectives on Cultural Studies Research on Aging. Research Report on the Academy Project “Religious and Poetic Constructions of Life Stages.” In: *Moderne. Kulturwissenschaftliches Annual* 6 (2010/2011): Aging.
- Elm, Dorothee/Fitzon, Thorsten/Liess Kathrin/Linden, Sandra (eds.) (2009): “The Old Man in Spring.” Creative Variations on Topoi in 18th- and 19th-Century Poetry. In: Age Topoi. Knowledge of the Stages of Life in Literature, Art, and Theology. Berlin, 187–219.
Conferences, workshops, and seminars organized as part of the project:
Conference: “Age Cutoffs. Time and Life Stages” (PDF) (September 23–25, 2009, Heidelberg)
Interdisciplinary Symposium: "Age Topoi. New Insights into Traditional Knowledge of Life Stages" (PDF) (March 13–14, 2008, Freiburg)
Faculty Members:
- Dr. Thorsten Fitzon
- Dr. Dorothee Elm von der Osten
- Dr. Kathrin Liess
- Dr. Sandra Linden
Neuroplasticity and Immunology in Cognitive Impairment in Old Age
Cognitive decline has traditionally been viewed as an inevitable consequence of the aging process. However, new findings from research on neuroplasticity suggest that this decline can be prevented—or even reversed to a certain extent—through behavioral training based on the principles of neuroplasticity. Consequently, methods for the earliest possible diagnosis of pathological aging processes—such as dementia—in combination with secondary preventive training measures are of increasing societal interest. The proposed project comprised three complementary subprojects in collaboration among the three applicants from the fields of neuropsychology, analytical chemistry, and clinical neurology/medicine. The project’s objectives were to develop and optimize methods for the early diagnosis of dementia and to test the feasibility and effectiveness of training interventions in older adults at high risk for dementia.
Publications resulting from the project:
Maftei M., Thurm F., Schnack C., Tumani H., Otto M., Elbert T., Kolassa I.T., Przybylski M., Manea M., von Arnim C.A. (2013). Increased levels of antigen-bound β-amyloid autoantibodies in serum and cerebrospinal fluid of Alzheimer’s disease patients. PLoS One 8(7): e68996.
Lebedeva E., Stingl J.C., Thal D.R., Ghebremedhin E., Strauss J., Özer E., Bertram L., von Einem B., Tumani H., Otto M., Riepe M.W., Ludolph A.C., von Arnim C.A. (2012). Genetic variants in PSEN2 and their correlation with CSF β-amyloid42 levels in AD, Neurobiol. Aging 33(1): 201.
Maftei M., Thurm F., Leirer V.M., von Arnim C.A., Elbert T., Przybylski M., Kolassa I.T., Manea M. (2012). Antigen-bound and free β-amyloid autoantibodies in the serum of healthy adults. PLoS One 7(9): e44516.
Maftei M., Tian X., Manea M., Exner T.E., Schwanzar D., von Arnim C.A., Przybylski M. (2012). Interaction structure of the complex between the neuroprotective factor humanin and the Alzheimer’s beta-amyloid peptide revealed by affinity mass spectrometry and molecular modeling. J. Pept. Sci. 18: 373–382.
Schlee W., Leirer V., Kolassa IT., Elbert T. (2012a). Age-related changes in neural functional connectivity and their behavioral relevance. BMC Neurosci. 13(1): 16.
Schlee W., Leirer V., Kolassa S., Thurm, F., Elbert, T., Kolassa I.T. (2012b). Development of Large-Scale Functional Networks over the Lifespan. Neurobiol Aging 33(10): 2411–21.
Watabe-Rudolph M., Song Z., Lausser L., Schnack C., Begus-Nahrmann Y., Scheithauer M.O., Rettinger G., Otto M., Tumani H., Thal D.R., Attems J., Jellinger K.A., Kestler H.A., von Arnim C.A., Rudolph K.L. (2012). Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer’s disease. Neurology 78: 569–577.
Leirer V.M., Wienbruch C., Kolassa S., Schlee W., Elbert T., Kolassa I.T. (2011). Changes in cortical slow-wave activity in healthy aging. Brain Imaging and Behavior 5(3): 222–228.
Thurm F., Scharpf A., Liebermann K., Kolassa S., Elbert T., Lüchtenberg D., Woll A., Kolassa I.T. (2011). Improvement of cognitive function after physical movement training in institutionalized very frail older adults with dementia. Journal of Gerontopsychology and Geriatric Psychiatry 24(4): 197–208.
Uttner I., Schurig N., von Arnim C.A., Lange-Asschenfeldt C., Brettschneider J., Riepe M.W., Tumani H. (2011). Amyloid beta 1-42 in cerebrospinal fluid is associated with cognitive plasticity. Psychiatry Research 190(1): 132–136.
von Einem B., Rehn F., Schwanzar D., Beyer A.S., Weber P., Wagner M., Schneckenburger H.. von Arnim C.A. (2010). Competition between the low-density lipoprotein receptor-related protein (LRP) and amyloid precursor protein (APP) for beta-secretase. Experimental Neurology 225(1): 85–93.
Jesse S., Brettschneider J., Süssmuth S.D., Landwehrmeyer B.G., von Arnim C.A., Ludolph A.C., Tumani H., Otto M. (2010). Summary of routine cerebrospinal fluid parameters in neurodegenerative diseases. Journal of Neurology 58(6): 1034–1041.
Leirer V.M., Wienbruch C., Paul-Jordanov I., Kolassa S., Elbert T., Kolassa I.T. (2010). Hippocampal activity during the transverse patterning task declines with cognitive competence but not with age. BMC Neuroscience 8(11): 113.
Drochioiu G., Manea M., Dragusanu M., Murariu M., Dragan E.S., Petre B.A., Mezó G., Przybylski M. (2009). Interaction of the beta-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study. Biophys Chem. 144(1/2): 9–20.
Fellow Research Fellows
Prof. Dr. Iris-Tatjana Kolassa
Dr. Marilena Manea
Prof. Dr. Christine von Arnim