Fountain of youth cells in the brain?
The hypothalamus is an almond-sized structure that sits in the lower, middle portion of the brain. It consists of a variety of different nuclei that regulate different aspects of behavior including thirst, hunger, body temperature, fatigue, sleep, and circadian rhythms as well as parenting and other attachment relationships. The hypothalamus produces specific neurohormones (called releasing hormones) that help regulate homeostatic processes in the body. Recently, scientists have discovered that the hypothalamus also regulates the aging process.
Neural stem cells are cells in the brain that have the capacity to develop into the cells of the nervous system – both neurons and glia (support cells of the nervous system). Neural stem cells are most prominent during embryonic development, but some persist into adulthood helping the brain to grow and develop as we age. In adulthood, neural stem cells are present in only a few regions, namely, the subventricular zone and the dentate gyrus of the hippocampus. Recently, neural stem cells were found in another region, the mediobasal nucleus of the hypothalamus. A group of scientists at the Albert Einstein College of Medicine in Bronx, NY set out to determine whether these hypothalamic neural stem cells are involved in the aging process (https://pubmed.ncbi.nlm.nih.gov/28746310/).
First, they wanted to assess whether these cells decrease as we age or determine the progression of these cells over the aging process. To do this, they examined the cells using various stem cell biomarkers and then counted the numbers of these cells in different age groups of mice. They found that as we age, the number of neural stem cells in the hypothalamus gradually decreases, and by the time we reach old age, they are virtually eliminated.
This led them to examine whether the loss of these cells could be causing age-related changes. Therefore, they intentionally ablated or removed these cells and then tested various cognitive functions that normally decline with aging. Upon deletion of these new hypothalamic cells, the mice performed worse on a variety of tasks. Their physical performance declined – they showed a decrease in muscle endurance, treadmill performance, and coordination. Their learning and memory functions declined – they became worse at recognizing objects and learning and remember information in their environment. In addition, their social behaviors declined. Finally, they showed a significant decrease in their lifespan. Collectively, these studies indicated that the hypothalamic neural stem cells control the speed of aging.
The scientists then determined whether age-related declines in physical, cognitive, and social impairments could be rescued by the addition of new hypothalamic neural stem cells. By injecting neural stem cells into the hypothalamus of mid-aged mice, physical abilities, cognitive functioning, and social behaviors all improved. In addition, the lifespan of these animals was lengthened.
They then wanted to know exactly what was so special about these “fountain of youth” cells. What they found was that these cells secrete exosomal microRNAs (miRNAs). Exosomes are vesicles (like bubbles) that contain various biological components. They are secreted from cells and are involved in transferring information to other cells, that is, they are involved in cell-to-cell communication. miRNAs are small, non-coding ribonucleic acids that help regulate gene expression or the translation of our genetic code into proteins. Therefore, exosomal miRNAs are exosomes that carry miRNAs and help carry this information and affect gene expression in a variety of cells throughout the brain and body. The scientists discovered that by experimentally decreasing the levels of these secreted particles, they could accelerate the aging process. Conversely (and excitingly), increasing levels of these exosomal miRNAs protected against the aging process.
In conclusion, this new research shows that hypothalamic neural stem cells and the substances they secrete regulate the aging process throughout the whole body. This is certainly not the whole story, but it is one tantalizing piece of the puzzle. Future studies will be needed to examine the actual function of the secreted miRNAs and how they contribute to keeping us young.
Resources:
Zhang, Yalin et al. “Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.” Nature vol. 548,7665 (2017): 52-57. doi:10.1038/nature23282
