NASA performed the first study of its kind with two identical twins, where one twin, Scott Kelly, lived on the International Space Station (ISS) for a full year, while his twin brother, Mark Kelly, stayed on Earth. Both identical twins were subjects to a wide range of test and investigations before, during and after the mission. The aim of this study was to gain further insight into the effects of extended time in space on the human body. It was found that many aspects of human physiology are impacted, which is not surprising per se. Staying in space, after all, is a tremendous amount of stress and the body needs to adapt.

However, some of the results are immensely interesting. The preliminary analysis of the collected data found that telomers are profoundly affected by staying in space. Telomers are the endings of the chromosomes and their function is to protect the coding DNA of the chromosomes from truncation during cell replication. This truncation of the DNA is an intrinsic characterisation of cell replication and happens with every replication. Telomers do not contain coding DNA and telomer shortening does not affect cell functions in general. However, when telomers become too short the cell often enters programmed cell death. Research suggests that shortened telomers are linked to age-related ailments and diseases (1). Scott Kelly’s stay in space significantly increased his telomer length, albeit it decreased to approximately pre-flight length within 48 hours of landing on earth. Telomer lengthening would essentially suggest a beneficial impact on health but it is hard to speculate whether this is actually the case, especially since the lengthening reversed so quickly after Scott Kelly’s return to Earth.

Scott Kelly (right) together with his brother, former astronaut, Mark Kelly (left).

Investigation on gene expression also indicated that Scott Kelly experienced higher levels of stress during his stay in space. However, it is somewhat unclear which DNA exactly has been investigated. One article states that the DNA and RNA of white blood cells has been used (https://www.nasa.gov/feature/how-stressful-will-a-trip-to-mars-be-on-the-human-body-we-now-have-a-peek-into-what-the-nasa) and another states cell-free DNA (https://www.nasa.gov/feature/nasa-twins-study-investigators-to-release-integrated-paper-in-2018) – cell free DNA contains DNA from white blood cells but also from other cells. Eventually, we need to wait for the publication of the actual research. Nevertheless, some genes were found to be differentially expressed only after spaceflight and were therefor labelled “space genes”. The alterations infer changes in several biological pathways in the cells. The impacted pathways are associated with: 1) tissue oxygenation and increased levels of carbon dioxide in the blood, 2) increased mitochondrial stress and increased occurrence of mitochondria in the blood, which indicates some form of damage to the mitochondria, 3) DNA damage repair, potentially caused by higher levels of radiation but also by Scott Kelly’s caloric restriction during his time in space, 4) bone formation, due to zero gravity, and 5) a hyperactive immune system, potentially caused by the different environment at the International Space Station. The majority of these changes in gene expression returned to post-flight levels but, surprisingly, 7 % of the astronaut’s gene expression remained disrupted 6 months after his return to Earth. This suggest possible longer-term changes induced by staying in space for one year.

Epigenetic investigations found an altered methylation pattern in several regions of the DNA of Scott’s white blood cells while he was on the ISS. These alterations returned to pre-flight state upon Scott’s return to Earth. This again could indicate potential genome damage that occurred in space. However, the results still need to be analysed.

Cytokine levels in Scott’s blood, which is a marker for inflammation, indicated increased inflammation. One set of cytokines was increased throughout his stay in space and another set of cytokines was increased right after his return to Earth. The latter even remained increased for six months. Additionally, certain proteins that are involved in maintaining normal insulin activity after meals were found to be increased. However, no speculations on the consequences have been made.

On the other side, staying in space for one year did not affect cognition, shown by several different tests. Neither was the immune systems response to a flu vaccine affected. The immune response of both twins to the flu vaccination was comparable and both showed increased levels immune cell production. This seems somewhat contrary to the gene expression investigations that suggested a hyperactive immune system.

Although, the gut microbiome differed pre-flight and during Scott’s stay in space, notably the bacterial taxa Bacteroidetes, one of the dominant phyla of the human gut microbiome (2), was decreased, the alterations did not persist upon his return to Erath. Overall, the changes were attributed to the change in diet during the stay at the ISS.

Cognitive investigations found that Scott Kelly’s speed and accuracy were decreased post-flight. This could, however, be attributed to exposure and adaption to Erath’s gravity.

This study aimed to gain further insight into the effects of extended time in space on the human body and contribute to the discovery of methods and technologies to support the safety of astronauts and their performance before, during and after space travel and exploration.

The preliminary publication of the results is vague, however draw interest and attention to the actual publication that is planned to be released by NSA 2018. So, stay tuned for further blog post on this exceptionally interesting study.

References

1. Eisenberg, D.T. (2011) An evolutionary review of human telomere biology: the thrifty telomere hypothesis and notes on potential adaptive paternal effects. Am J Hum Biol. 23(2):149-67.

2. Johnson, E. L., Heaver, S. L., Walters, W. A., & Ley, R. E. (2017) Microbiome and metabolic disease: revisiting the bacterial phylum Bacteroidetes. Journal of Molecular Medicine, 95(1): 1-8.

Lion’s mane (scientifically Hericium erinaceus) is an edible mushroom that has been used in traditional Chinese medicine for a long time. In recent years, this white, globular-shaped and rotund mushroom has been investigated for its beneficial effects on humans, especially for its neuron growth promoting effects in the brain (neurogenesis).

Could it be that lion’s mane has an actual effect on neuron growth, or is it just another disappointing “miracle drug” and temporary hype?

Biochemical analysis of lion’s mane mushroom found a wide variety of bioactive compounds, but two compounds in particular caught the attention of researchers: hericenones and erinacines. Both compounds have been shown to induce Nerve Growth Factors (NGFs) biosynthesis in nerve cells. NGFs activate cell differentiation and promote growth of neurons, as well as re-myelination of neurons. Myelin is an essential component of neurons and crucial for their function (1).

NGF belongs to the protein family of neurotrophins. Research data strongly suggests that neurotrophins are essential factors for the survival and differentiation of nerve cells. Decreased production of neurotrophins seems to be involved in the development of neurodegenerative diseases.

Neurotrophins would have been interesting compounds in treating neurodegenerative diseases, however, their high molecular weight prevents them from crossing the blood-brain barrier, and thus reaching the brain. The NGF-inducing hericenones and erinacines in lion’s mane mushrooms, on the other hand, seem to cross the blood brain barrier, and thus induce growth of neurons in the brain (2).

Investigations in cell cultures showed increased expression of genes that are associated with NGF synthesis upon administration of several erinacines from lion’s mane mushrooms. It was found that these compounds potentiate NGF-induced outgrowth from neurons. This added to the perception that lion’s mane mushroom affects survival and differentiation in nerve cells and displays anti-dementia activity. Therefore, intake of lion’s mane mushroom could potentially reduce the risk of developing neurodegenerative diseases (2).

In a study with rats, erinacine administration resulted in an upregulation of NGF in two brain areas, the locus caeruleus and the hippocampus. These brain areas are usually affected in patients with dementia and Alzheimer’s disease. In accordance with these results, erinacine administration in mice that exhibit symptoms equal to Alzheimer’s and Parkinson’s disease ameliorated the symptoms of both diseases (2,3,4).

Mice with impaired learning and memory that were fed lion’s mane mushrooms performed better in a memory test compared to mice that were not given the mushroom. The mice also regained a sense of curiosity and spend more time exploring novel objects. These results indicate that lion’s mane mushroom administration improves cognitive impairments and could be utilised in the treatment of cognitive dysfunctions such as Alzheimer’s disease (5).

In a 23 days study, mice were injected with a compound called amyloid ß peptide directly into the fluid in the brain which led to impaired learning and memory in these mice, specifically impaired spatial short-term and visual recognition memory. Administration of lion’s mane mushrooms, however, resulted in better performance in a memory test, accompanied by regaining a sense of curiosity in these memory-impaired mice. The mice spend more time exploring novel objects than mice that were not given lion’s mane mushroom. Examination of the mice brains revealed amyloid plaque formation similar to the one observed in Alzheimer’s patients. Amyloid plaques are involved in inflammation of brain tissue, impair neuron transmission, and associated with nerve degeneration. It is believed that amyloid plaque formation is a marker for Alzheimer’s disease. Overall, these results indicate that lion’s mane mushroom administration improves cognitive impairments linked to amyloid plaque formation. Lion’s mane mushroom could be utilised in the treatment of cognitive dysfunctions such as Alzheimer’s disease. However, lion’s mane represented 5 % of the whole mouse diet, which would translate to a substantial amount of daily human food intake. (5).

These results are promising, but, in fact, results obtained in the mouse model do not necessarily translate to humans. Fortunately, the effects of lion’s mane mushroom have also been studied in humans.

In a 16 weeks investigation with 30 Japanese men and women between the age of 50 to 80, who exhibited mild cognitive impairment, lion’s mane administration substantially improved their cognitive function. The men and women were tested at weeks 8, 12 and 16 and showed significantly higher scores in cognitive function tests than the control group. Crucially, the cognitive function increased with the duration of lion’s mane mushroom intake. The differences to the control group were greatest at week 16. During the investigation, the subjects were given 250 mg of lion’s mane mushroom daily. However, the beneficial effects decreased after the administration of lion’s mane mushroom was discontinued. The researchers thus concluded that a continuous intake is necessary to maintain the beneficial effects on cognitive functions. The researchers speculated that the promotion of NGF synthesis by compounds in lion’s mane could contribute to the prevention or alleviation of Alzheimer’s disease (6).

An important point that should not be disregarded is the palatability of lion’s mane mushroom. Ingestion of the mushroom itself does not present a health risk even after long-term consumption. However, some people have reported mild troubles with digestion but not to the point where intake has to be discontinued (6).

Overall, the research results are promising, and lion’s mane could contribute to the prevention or at least mitigation of cognitive impairment diseases. With increasing age, everybody will eventually suffer from cognitive impairment in some sort. Maintaining cognitive faculties would enhance the personal quality of life as well as the community’s quality of life.

Another very interesting area for research would be the impact of lion’s mane mushroom on healthy individuals. Would the mushroom-derived promotion of NGF synthesis actually improve cognitive functions? It is hard to speculate on the impact and further investigations are necessary to draw conclusions.

References

1. Lai PL, Naidu M, Sabaratnam V, Wong KH, David RP, Kuppusamy UR, Abdullah N, Malek SN. (2013) Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int J Med Mushrooms. 15(6):539-54.

2. Zhang, C.-C., Cao, C.-Y., Kubo, M., Harada, K., Yan, X.-T., Fukuyama, Y., & Gao, J.-M. (2017). Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway. International Journal of Molecular Sciences, 18(8), 1659.

3. Tsai-Teng, T., Chin-Chu, C., Li-Ya, L., Wan-Ping, C., Chung-Kuang, L., Chien-Chang, S., Chi-Ying, H.F., Chien-Chih, C., Shiao, Y.J. (2016) Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice. J. Biomed. Sci. 23(1):49.

4. Kuo, H.C., Lu, C.C., Shen, C.H., Tung, S.Y., Hsieh, M.C., Lee, K.C., Lee, L.Y., Chen, C.C., Teng, C.C., Huang, W.S., et al. (2016) Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade. J. Transl. Med. 14:78.

5. Mori, K., Obara, Y., Moriya, T., Inatomi, S., Nakahata, N. (2011) Effects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Biomed. Res. 32(1):67-72.

6. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. (2009) Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 23(3):367-72.