Population prognostics show that by the year 2030, 29% of the Danish population will be 60+ years compared to 24% today and that much of this increase will be due to increased numbers of persons 80 years of age or more. Similar aging populations are seen world-wide. With this shift in population demographics, there is also increased prevalence of diseases related to aging. Why is age a risk factor for sustained damage following slight head trauma in the elderly and what mechanisms in brain ageing makes the brain frail and predisposes to neurodegenerative diseases such as Alzheimer’s disease? That is the question.
Our first study showed that a concerted action among astrocytes in aged brains giving rise to astroglial calcium waves. These waves were abundant in old but not young brains and evoked small but repeated rises in oxygen consumption. This is one brain ageing mechanism with the potential to reduce brain's oxidative reserve capacity and thereby contribute to brain frailty.
Healthy brain aging is also characterized by reduced cerebral blood flow (CBF) and reduced responses to rises in neuronal activity – the supply of food for thought is restricted and even when the need goes up supply is at the borderline of being insufficient. Our second study reported that this was strongly correlated to reduced spontaneous and evoked gamma activity, which is strongly linked to perception, cognition and memory is humans as well as rodents. Gamma oscillations may drive the mechanisms responsible adjusting blood flow to brain activity, which decrease with age. In contrast, the coupling between metabolism and activity increase with age, despite reduced gamma oscillations in old animals. This could suggest that gamma activity and the interneurons that produce them are key players in healthy brain aging.
In our current project we use mice with parvalbumine (PV) positive interneurons that can be stimulated by light, so called optogenetic stimulation. This research project is believed to shed light on the importance of this particular type of interneuron in vascular and metabolic regulation in young and old mice.
- Thomsen K, Yokota T, Hasan-Olive MM, Sherazi N, Fakouri NB, Desler C, Regnell CE, Larsen S, Rasmussen LJ, Dela F, Bergersen LH, Lauritzen M. Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus. Neurobiol Aging. 2017.
- Mathiesen C, Brazhe A, Thomsen K, Lauritzen M: Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen. J Cereb Blood Flow Metab 2013;33:161-169.
- Brazhe A, Mathiesen C, Lauritzen M: Multiscale vision model highlights spontaneous glial calcium waves recorded by 2-photon imaging in brain tissue. Neuroimage 2013;68:192-202
- Jessen, S. B., C. Mathiesen, B. L. Lind and M. Lauritzen (2015). "Interneuron Deficit Associates Attenuated Network Synchronization to Mismatch of Energy Supply and Demand in Aging Mouse Brains." Cereb Cortex. 2015 Oct 29. pii: bhv261. [Epub ahead of print] PMID: 26514162