The Aging Cerebral Clock

How do you keep track of time? The watch on your wrist? The phone in your pocket? A calendar? A Sundial? Though the sun may seem like an antiquated timepiece in the modern world, that’s exactly what your body uses! Many, if not all, of our physiological processes exhibit circadian rhythms – daily patterns that correspond to the cyclic relationship of the Sun and Earth (1). Deep within our brain, there are specialized groups of neurons called the suprachiasmatic nuclei (SCN) that function like a biological clock. These neurons are found directly above the optic tract (the bundle of nerves that carries information from your eyes to your brain) and make sure that all of our daily biological activities occur on time. Collectively, these neurons regulate the sleep/wake cycle, physical activity and alertness, food-seeking behavior, and many of our other vital physiological processes (see Figure).

Asdownload we age, our circadian rhythms become less consistent and less pronounced. This is perhaps most evident in our daily sleep/wake cycle. Additionally, aged individuals also report problems in learning and memory. One theory for how our brain learns and stores memory, states that neurons must grow and make new connections with other neurons. This process, known as synaptogenesis, requires the production of new cellular building blocks – proteins. The blueprints for these new proteins come in the form of DNA and RNA. Previous work suggests that the aging brain has difficulty converting DNA to RNA, and that this process might explain why synaptogenesis declines with age (2).

A recent publication from Kwapis and colleagues suggests one possible mechanism relating these two observations (3). Their work indicates that the circadian gene Period1 (Per1) is vital to memory formation in the aging brain. Furthermore, restoration of Per1 transcription in the aging brain via deletion of a repressive DNA-binding protein (HDAC3) can improve performance of aged mice. Taken together their findings provide additional evidence that the molecular mechanisms responsible for circadian rhythms are vital to proper brain function.

Although it isn’t practical for us to delete the HDAC3 gene from our brains as we get older, maintaining a consistent daily rhythm is a bit easier. So do yourself a favor – soak up some sunshine, and try not to stay up all night watching Netflix.

  1. Pittendrigh, Colin S. (1993) Temporal organization: reflections of a Darwinian clock-watcher. Annual review of physiology 55, 17-54.
  2. Penner, M. R., Roth, T. L., Barnes, C. A. & Sweatt, J. D. (2010) An epigenetic hypothesis of aging-related cognitive dysfunction. Front Aging Neurosci. 2, 9.
  3.  Kwapis, Janine L., et al. (2018) Epigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory. Nature communications 9, 1-13.

Erik Hodges

Department of Biomolecular Sciences

University of Mississippi

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