Trehalose and Longevity
Summary
- Trehalose is a naturally occurring sugar found in various foods such as mushrooms, seaweed, and yeast.
- Trehalose is broken down by the enzyme, trehalase, found in the intestinal villi (finger-like projections), kidney brush border, liver, and blood.
- Trehalose displays antioxidant properties by activating components that combat oxidative stress in cells.
- Trehalose promotes autophagy.
- Trehalose can reduce inflammaging.
- Trehalose can reduce the accumulation of proteins, which is toxic to cells and is a hallmark of aging (loss of proteostasis).
- Trehalose may reduce arterial stiffness that occurs with aging.
- Trehalose supports healthy aging in the brain, liver, and kidney in older adults.
Trehalose Impacts Aging Via:
- Loss of proteostasis
- Disabled macroautophagy
- Inflammaging
- Altered cellular communication
- Mitochondrial dysfunction
The Role of Trehalose in Aging and Longevity
Trehalose is a naturally occurring sugar that consists of two molecules of glucose, also known as a non-reducing disaccharide. It is commonly found in foods such as mushrooms, seaweed, and yeast. Some bacteria, fungi, plants, and invertebrate animals use trehalose as a storage carbohydrate much like a glycogen store in humans.
Trehalose Versus Sucrose
Sucrose is another common naturally-occurring disaccharide found in fruits, vegetables, and nuts. It is also the main constituent of white sugar.
Sucrose is made of one molecule of fructose and one molecule of glucose. When used as a dietary sugar, trehalose may offer advantages over sucrose in helping maintain balanced blood glucose levels. In a study involving healthy individuals, those who consumed trehalose had lower post-meal blood glucose levels than those who consumed sucrose. (Yoshizane, et.al., 2020)
Trehalose and Aging
Trehalose has gained attention as an anti-aging ingredient because of its antioxidant properties and ability to restore cells’ autophagy processes.
Research shows that trehalose supplementation promotes autophagy, which is disabled in cells of an aging body, by activating autophagy-related proteins and pathways. (Castillo et. al., 2013, Lotfi et. al., 2018, McCarthy et. al., 2019, Pan et. al., 2022)
Trehalose also functions as an antioxidant by activating a cellular pathway known as the p62-Keap1/Nrf2 pathway. This pathway plays a protective role in cells by responding to oxidative stress. Additionally, the same study revealed that supplementation with trehalose reduced the amount of reactive oxygen species. In high amounts, these can contribute to oxidative stress during aging. (Mizunoe et. al., 2018)
The Impact of Trehalose on Health
Aging affects all organ systems in the body, causing vital organ functions to decline slowly. However, research has shown that trehalose has protective effects on the brain, liver, and kidneys of older adults. Supplementing may restore the cellular processes that maintain the balance of proteins, prevent oxidative stress, and ensure metabolic function.
Trehalose and Brain Health
As people age, the brain naturally changes in size, blood flow, and function, affecting memory, learning, and other cognitive functions. Research shows that consuming trehalose may delay brain aging and boost cognitive functions like learning and memory. (Sun et. al., 2020)
Alzheimer’s disease (AD) is an age-related neurodegenerative disease. Researchers found that trehalose may support brain health by facilitating the removal of protein clumps in the brain — one of the hallmarks of AD — through autophagy. (Krüger et. al., 2012, Pan et. al., 2022)
Moreover, scientists discovered that trehalose supports brain health as we age. It helps delay age-related cognitive decline in a way similar to the effects of exercise. This happens through the regulation of proteins involved in autophagy, the body’s natural cellular cleanup process. (Pan et. al., 2022)
Research has also suggested that trehalose possess antioxidant properties by protecting cells against oxidative stress.
In a recent study, researchers demonstrated the anti-aging role of trehalose. It activated genes related to the Nrf2 pathway — a major regulator of the body’s antioxidant defenses. By doing so, trehalose helped protect cells from oxidative stress. This same study also found that consuming trehalose once a day for eight weeks helped to boost cognitive function. After eight weeks, there was a significant improvement in learning and memory impairment. (Sun et. al., 2020)
Scientists also discovered that daily trehalose supplementation for 30 days can support brain health. It works by restoring the cells’ antioxidant systems and reducing inflammation in the brain. These effects are linked to increased production of sirtuins like SIRT1 and the activation of microRNA, a type of non-coding RNA involved in regulating SIRT1 expression. (Shafiei et. al., 2023) SIRT1 is involved in regulating inflammatory responses in the body.
Trehalose and Kidney Health
Kidney function gradually declines as a person ages, which can lead to kidney disease. Increased oxidative stress during the aging process can damage organs like the kidney, exacerbating the development of age-related kidney diseases.
Trehalose has been shown to provide antioxidant benefits that help support kidney health as we age. In a recent study, daily trehalose supplementation for one month reduced age-related damage to the kidney’s antioxidant systems. This effect was linked to increased activity of proteins that protect cells from oxidative stress (Hozhabri et al., 2022). (Hozhabri et. al., 2022)
The antioxidant effect of trehalose supplementation was also demonstrated in another study. Researchers found that when consumed daily over one month, trehalose helped to boost kidney health in older study subjects. Furthermore, they discovered that trehalose supports healthy kidneys by reducing age-related oxidative stress and inflammation through a sirtuin protein, SIRT1. This protein is normally involved in regulating inflammation, repairing DNA damage, and improving metabolic function. (Bahri et. al., 2021)
Trehalose and Liver Health
Aging is associated with an increased risk of age-related liver diseases, like non-alcoholic fatty liver disease, due to changes in the liver’s metabolic functions.
Daily trehalose supplementation for one month helped to maintain liver health. It increased cellular components related to metabolism, helping to prevent fat buildup in the liver. This effect may offer a promising strategy to slow the age-related decline in liver function (Naiini et. al., 2023)
Beyond preventing fat accumulation, trehalose supplementation for four weeks suppresses inflammatory signals and maintains the liver’s balance of cellular proteins. (Pagliassotti et. al., 2017)
Trehalose and Cardiovascular Health
Arterial stiffness occurs with aging and is associated with the progression to more serious and life-threatening cardiovascular diseases.
Trehalose when taken orally every day for 12 weeks by middle-aged and older adults demonstrated benefits towards cardiovascular health. The trehalose supplementation helped to improve the resistance artery function – a major risk factor for cardiovascular disease. Scientists postulate that this could be due to an increase in the amount of and response to nitric oxide, a blood vessel dilator that helps to reduce blood pressure. (Kaplon et. al., 2016)
Other studies also support this by showing that trehalose supplementation decreased arterial stiffness through restoring autophagy in study subjects with high blood pressure (hypertension). (McCarthy et al., 2019)
NOVOS VITAL & Trehalose
NOVOS Vital contains 4 grams of this powerful ingredient, trehalose, along with six other scientifically researched ingredients that target vital organ health. Together, these ingredients work to optimize your brain, eyes, gut, kidneys, liver, muscles, and heart. NOVOS Vital is a low calorie and low sugar chew that provides a healthy alternative for a sweet treat.
References
Bahri, F., Khaksari, M., Movahedinia, S., Shafiei, B., Rajizadeh, M. A., & Nazari-Robati, M. (2021). Improving SIRT1 by trehalose supplementation reduces oxidative stress, inflammation, and histopathological scores in the kidney of aged rats. Journal of food biochemistry, 45(10), e13931. https://doi.org/10.1111/jfbc.13931
Castillo, K., Nassif, M., Valenzuela, V., Rojas, F., Matus, S., Mercado, G., Court, F. A., van Zundert, B., & Hetz, C. (2013). Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy, 9(9), 1308–1320. https://doi.org/10.4161/auto.25188
Hozhabri, Y., Sadeghi, A., Nazari-Robati, M., Bahri, F., Salimi, F., Abolhassani, M., & Mohammadi, A. (2022). Effects of trehalose on NFE2L2, catalase, and superoxide dismutase in the kidney of aged rats. Molecular biology research communications, 11(1), 29–36. https://doi.org/10.22099/mbrc.2022.42014.1688
Kaplon, R. E., Hill, S. D., Bispham, N. Z., Santos-Parker, J. R., Nowlan, M. J., Snyder, L. L., Chonchol, M., LaRocca, T. J., McQueen, M. B., & Seals, D. R. (2016). Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults. Aging, 8(6), 1167–1183. https://doi.org/10.18632/aging.100962
Krüger, U., Wang, Y., Kumar, S., & Mandelkow, E. M. (2012). Autophagic degradation of tau in primary neurons and its enhancement by trehalose. Neurobiology of aging, 33(10), 2291–2305. https://doi.org/10.1016/j.neurobiolaging.2011.11.009
Lotfi, P., Tse, D. Y., Di Ronza, A., Seymour, M. L., Martano, G., Cooper, J. D., Pereira, F. A., Passafaro, M., Wu, S. M., & Sardiello, M. (2018). Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency. Autophagy, 14(8), 1419–1434. https://doi.org/10.1080/15548627.2018.1474313
McCarthy, C. G., Wenceslau, C. F., Calmasini, F. B., Klee, N. S., Brands, M. W., Joe, B., & Webb, R. C. (2019). Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats. American journal of physiology. Heart and circulatory physiology, 317(5), H1013–H1027. https://doi.org/10.1152/ajpheart.00227.2019
Mizunoe, Y., Kobayashi, M., Sudo, Y., Watanabe, S., Yasukawa, H., Natori, D., Hoshino, A., Negishi, A., Okita, N., Komatsu, M., & Higami, Y. (2018). Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways. Redox biology, 15, 115–124. https://doi.org/10.1016/j.redox.2017.09.007
Naiini, M. R., Shahouzehi, B., Azizi, S., Shafiei, B., & Nazari-Robati, M. (2023). Trehalose-induced SIRT1/AMPK activation regulates SREBP-1c/PPAR-α to alleviate lipid accumulation in aged liver. Naunyn-Schmiedeberg’s archives of pharmacology, 10.1007/s00210-023-02644-w. Advance online publication. https://doi.org/10.1007/s00210-023-02644-w
Pagliassotti, M. J., Estrada, A. L., Hudson, W. M., Wei, Y., Wang, D., Seals, D. R., Zigler, M. L., & LaRocca, T. J. (2017). Trehalose supplementation reduces hepatic endoplasmic reticulum stress and inflammatory signaling in old mice. The Journal of nutritional biochemistry, 45, 15–23. https://doi.org/10.1016/j.jnutbio.2017.02.022
Pan, S., Guo, S., Dai, J., Gu, Y., Wang, G., Wang, Y., Qin, Z., & Luo, L. (2022). Trehalose ameliorates autophagy dysregulation in aged cortex and acts as an exercise mimetic to delay brain aging in elderly mice. Food Science and Human Wellness, 11(4), 1036–1044. https://www.sciencedirect.com/science/article/pii/S2213453022000325?via%3Dihub
Shafiei, B., Afgar, A., Nematollahi, M. H., Shabani, M., & Nazari-Robati, M. (2023). Effect of trehalose on miR-132 and SIRT1 in the hippocampus of aged rats. Neuroscience letters, 813, 137418. https://doi.org/10.1016/j.neulet.2023.137418
S N Chaitanya, N., Devi, A., Sahu, S., & Alugoju, P. (2021). Molecular mechanisms of action of Trehalose in cancer: A comprehensive review. Life sciences, 269, 118968. https://doi.org/10.1016/j.lfs.2020.118968
Sun, L., Zhao, Q., Xiao, Y., Liu, X., Li, Y., Zhang, J., Pan, J., & Zhang, Z. (2020). Trehalose targets Nrf2 signal to alleviate d-galactose induced aging and improve behavioral ability. Biochemical and biophysical research communications, 521(1), 113–119. https://doi.org/10.1016/j.bbrc.2019.10.088
Yoshizane, C., Mizote, A., Arai, C. et al. Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers. Nutr J 19, 68 (2020). https://doi.org/10.1186/s12937-020-00586-0
