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 are all at play, making it necessary for various scientific disciplines to collaborate in order to address the complex challenges that arise as a result.
Yet there are significant cultural differences in the cognitive framing of these findings, some of which are only established through performance: what constitutes youth, and what constitutes old age?
Subprogram 3 investigated the biological, social, and cultural aspects of the human life cycle and was successfully completed in 2012.
The joint closing conference titled "The Human Life Cycle – Biological, Social, and Cultural Aspects" (PDF)took place on June 14–15, 2012, in Heidelberg.
Supported by
Changes in Memory Function in the Aging Brain: Functional, Biochemical, and Genetic Aspects
As part of the project’s multimodal approach, significant insights were gained into 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 processes (compensation) with increasing age. Structurally, the extent 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), significant 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 neural activity in 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 changes in memory-related networks over the lifespan. 20th Annual Computational Neuroscience Meeting: CNS, Stockholm, Sweden. BMC Neuroscience 12 (Suppl. 1): 71.
Fellow students:
- Dr. Carsten Diener
- Dr. Franziska Matthäus
Associate project partners
- Assistant Professor Gabriela Ende, Ph.D.
- 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 life, 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 aim 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 of Applied Mathematics allowed for the integration of medical, biological, and mathematical aspects to conduct a comprehensive investigation from various perspectives. The study was based on the assumption that the biological mechanisms of the human life cycle are less dependent on the random accumulation of errors in cellular metabolism and are instead predetermined within our stem cells as part of a meaningful and predetermined “aging program.” The results of the work revealed a connection between replicative senescence and a continuous change in their stem cell potential as well as in the 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 and 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 During 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., and 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 using 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.
Fellow students:
- Dr. Simone Bork
- Dr. Anna Marciniak-Czochra
- PD Dr. Stefan Pfister
Associate project partner:
Prof. Dr. Dr. Wolfgang Wagner
Religious and Poetic Constructions of Age. Conceptualizing and Interpreting Age-Related Milestones in the Life Cycle
The wide variability of aging in humans also influences cultural understandings of the aging process and the stages of life. The demographic changes of the present day were initiated by a steady increase in life expectancy over the past 150 years. On the one hand, the connection between reproduction, senescence, and mortality—as initially assumed by evolutionary biology—seems increasingly questionable due to the extended life cycle; on the other hand, however, cognitive conceptions of the life cycle have changed comparatively little. Thus, biomedical empirical 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 modern times, traditional, pre- 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 life stages within a long historical perspective. Subsequently, the study examined the rules by which these concepts were cognitively modeled and how they relate to one another today. The period of investigation spanned from the time of the Old Testament to recent literature 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, cultural interpretive spaces for the human life course emerged from the partly topical descriptive patterns in religious and poetic texts, and how this enabled a transformation in discourses on age that, on the one hand, drew upon traditional conceptual frameworks while, at the same time, transcending and renewing them through contextual and performative variation.
Publications resulting from the project:
- Elm,Dorothee/Fitzon,Thorsten/Liess, Kathrin (2012): From the Wise to the Lived Old Age. Variations on a Theme. 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 Jahrbuch* 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: Alterstopoi. 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 Age" (PDF) (September 23–25, 2009, Heidelberg)
Interdisciplinary Symposium: "Alterstopoi: New Insights into Traditional Knowledge of the Stages of Life" (PDF) (March 13–14, 2008, Freiburg)
Fellow students:
- Dr. Thorsten Fitzon
- Dr. Dorothee Elm von der Osten
- Dr. Kathrin Liess
- Dr. Sandra Linden
Neuroplasticity and Immunology in Cognitive Impairment in Older Adults
Cognitive decline has traditionally been viewed as an inevitable consequence of the aging process. However, new findings in plasticity research suggest that this decline can be prevented—or even reversed to a certain extent—through behavioral training based on 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 the development and optimization of methods for the early diagnosis of dementia, as well as the testing of the feasibility and effectiveness of training measures 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 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. Neurobiology of 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 exercise 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.
by 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 ability 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 spectrometry model study. Biophys Chem. 144(1/2): 9–20.
female colleagues
Prof. Dr. Iris-Tatjana Kolassa
Dr. Marilena Manea
Prof. Dr. Christine von Arnim