Along with preventing metabolic syndrome and its aftermath …
New research has found that cinnamon bark can extend C. elegans’ lifespan.
Could it do the same for humans?
By Will Block
Bob Goldstein, UNC Chapel Hill,
orms have played an important role in life extension research. As an example, the mutation of a single-gene in nematodes (Caenorhabditis elegans) was found to significantly extend their lifespans—by a factor of two—as research conducted by Cynthia Kenyon, Ph.D., revealed back in 1993. About the significance of animal models, Dr. Kenyon has said, “We know now, however, that the ageing process, like so many other biological processes, is subject to regulation by classical signaling pathways and transcription factors. Many of these pathways were first discovered in small, short-lived organisms such as yeast, worms and flies, but a remarkable fraction turns out to extend lifespan in mammals as well.” Humans are mammals.
The Worm Continues to Turn
In new research, carried out by a team of researchers at the University of Maryland in Baltimore, a biological method has been created that can uncover the power of herbs, even showing that they can extend lifespan. Using tiny C. elegans worms that live a mere 20 days, researchers have managed to determine which compounds found in two common Chinese herbal formulations have a potential for extending life expectancy. Of the herbs examined, cinnamon and ginseng were found to show the most promise.
Longevity Benefits from Cinnamon and Ginseng
Led by Yuan Luo, Ph.D., the researchers conducted a systematic evaluation of a traditional Chinese medicine called Shi-Quan-Da-Bu-Tang (SQDB) containing 10 herbs—reportedly effective for fatigue and energy—and another formulation called Huo Luo Xiao Ling Dan (HLXL) containing 11 herbs—used as a treatment for arthritic joint pain. Both mixtures are reputed to have benefits for healthy living and longevity in humans.
The researchers tested the mixtures, as well as each separate herb in them, on the laboratory worm C. elegans, considered the “lab rat” for research of this kind because it shares genes for aging and other traits with humans. C. elegans also shares high similarities with human biochemical pathways. What they found was astonishing. Cinnamon bark (Cinnamomum cassia) from HLXL extended the lifespan of the worms by 14.5 percent, while the cinnamon bark from SQDB worked well also, extending lifespan by 10.8 percent. The researchers also found that ginseng root (Panax ginseng) from SQDB extended life span by 7.7 percent. Ginseng is not an ingredient in the HLXL formulation. While translating the findings of lifespan extension from worm to humans is currently unwarranted, there is substantial experimental evidence suggesting that drugs which extend lifespan in animal models are extremely useful in treatment of age-related diseases, including cancer and neurodegenerative diseases in humans. It could be similar for herbs.
Hydrogen Peroxide, Heat Shock Proteins, and Alzheimer’s Disease
To identify the underlying mechanisms, the researchers noted that cinnamon and ginseng, along with the SQDB formulation, reduced levels of hydrogen peroxide, a known destroyer of cells. Cinnamon, ginseng, and SQDB also enhanced expression of heat shock proteins, a class of functionally related proteins, the expression of which is increased when cells are stressed. Their activation can play an important role in maintaining cell functions.
Especially interesting, the lifespan-extending herbs significantly reduced the worm’s expression of amyloid, a toxicity factor that is a hallmark in the human brain of the pathological development of Alzheimer’s disease. Cinnamon extract has previously been found to inhibit tau aggregation, another hallmark associated with Alzheimer’s disease and with the formation of neurofibrillary tangles, one-half of the dreaded team of “plaques and tangles” that degrade, and ultimately destroy, significant portions of the brains of Alzheimer’s victims.
Life Extension and Pathways
As the paper points out, even though many Americans use herbs—a national survey published in the JAMA in 1998 found that 49 percent of American adults had used herbal medicines within the previous year—proof of their efficacy is extremely difficult, as it is difficult to discern their modes of action in the body.
Thus the adaptation of the C. elegans model to the researchers’ investigatory goals can be viewed separately as an important achievement. To reemphasize a salient point, the worm has a high level of common genetic origins that are found in humans. But yet, the real challenge was to learn how to use the worm as a model system for studying gene-environment interactions.
In their experiments, the researchers first used so-called “wild” C. elegans to screen the herbal mixtures and single herbs. They determined which herbs enhanced the lifespan of the worms, and then tested those herbs on well-characterized mutant worms. Each mutant was missing a single gene known for lifespan and/or stress resistance, specifically for insulin signaling, anti-oxidative, and serotonin signaling pathways.
Cinnamon has previously been shown to affect the insulin and antioxidant pathways (see sidebar, “Cinnamon Helps Prevent Metabolic Syndrome”). To date, however, there have only been two papers suggesting cinnamon’s impact on the serotonin signaling pathway. In the first paper, two active compounds that prevent serotonin-induced ulcers in rats were isolated from Chinese cinnamon (the same cinnamon used in the University of Maryland study), one of which [3-(2-hydroxyphenyl)-propanoic acid] worked at a remarkably low dose (40 micrograms/kg body weight). This compound also inhibited gastric ulcers induced by the other ulcer-causing agents. In the second study, Chinese cinnamon was found to inhibit both stress-related ulcers and gastric ulcers.
Cinnamon Helps Prevent Metabolic Syndrome
A recent review article on the power of cinnamon to help prevent insulin resistance, metabolic syndrome, and type 2 diabetes has just been published by celebrated researcher Richard A. Anderson, Ph.D., and colleagues. In this paper, cinnamon extract is appraised, based on the total amount of research done to date, on its ability of operate at various levels to help prevent and reverse the cascade of events that ultimately results in type 2 diabetes.
Of great concern to health maintenance is the growing obesity epidemic. Combined with a societal move away from exercise, these trends have led to what is termed metabolic syndrome. This condition is associated with insulin resistance, elevated glucose and lipids, decreased antioxidant activity, inflammation, and (to make matters worse) increased weight gain and increased glycation of proteins.
Fortunately, cinnamon has been championed in a cascade of in vitro, animal, and human studies to improve all of the above variables. To top things off, cinnamon has been shown to benefit Alzheimer’s disease by inhibiting and reversing tau formation in vitro. It has also been found to block cell swelling associated with ischemic stroke. Other in vitro studies show that the various compounds of cinnamon help to control angiogenesis, the growth of new blood vessels from pre-existing vessels required for the proliferation of cancer cells.
As well, human studies using subjects with metabolic syndrome, type 2 diabetes mellitus, and polycystic ovary syndrome all show beneficial effects from cinnamon, including positive effects on insulin, insulin sensitivity, glucose, and lipids. Also, these studies have reported improvement in blood pressure, antioxidant status, lean body mass, and gastric emptying.
Nevertheless, not all studies show positively for cinnamon. Dependent on the type and dose of cinnamon used, as well as the type of subjects and the drugs they are taking, the response to cinnamon varies. Yet in the recap, there is growing scientific support that cinnamon’s compounds play a crucial role in helping to alleviate and prevent metabolic syndrome, type 2 diabetes, not to mention cardiovascular and related diseases.
- Qin B, Panickar KS, Anderson RA. cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome, and type 2 diabetes. J Diabetes Sci Technol 2010 May 1;4(3):685-93.
Nutrigenomics Serves Cinnamon Research
Nutrigenomics is the study of the effects of foods and its constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins. Thus, it provides a basis for understanding the biological activity of food components. Nutrigenomics may also be thought of as the study of the influence of genetic variation on nutrition through the correlation of gene expression (or single-nucleotide polymorphisms) with a nutrient’s absorption, metabolism, elimination, and biological effects. It is the goal of nutrigenomics to develop scientific method to optimize nutrition, with respect to the subject’s genotype (the genetic constitution of a cell, an organism, or an individual).
As the evidence compiles, cinnamon and its compounds are reported to have beneficial effects on people with normal and the metabolic syndrome, impaired glucose tolerance, insulin resistance, and type 2 diabetes. Nonetheless, not all research is in agreement, and the molecular characterization of cinnamon’s effects is limited. So it is valuable to approach cinnamon from a nutrigenomics angle, which is what a new study has done, investigating the effects of cinnamon on gene expression in cultured mouse fat cells.
Using a water-soluble extract prepared from Cinnamomum burmannii, quantitative real-time polymerase chain reaction (PCR) was used to investigate cinnamon effects on the expression of genes coding for adipokines, glucose transporter family, and insulin-signaling components in mouse fat cells. In molecular biology, PCR is a laboratory technique used to amplify and simultaneously quantify a targeted DNA molecule. The shear benefit of its use is the detection and quantification of one or more specific sequences in a DNA sample, often when amounts of material are minute.
Cinnamon was found to increase glucose transporter and decrease the expression of further genes encoding insulin-signaling pathway proteins. This study indicates that cinnamon affects the expression of multiple genes in fat cells and this regulation may contribute to cinnamon’s potential health benefits.
- Cao H, Graves DJ, Anderson RA. Cinnamon extract regulates glucose transporter and insulin-signaling gene expression in mouse adipocytes. Phytomedicine 2010 May 27. [Epub ahead of print]
When Short Life is Important
Of principal importance to the research is the very short life cycle of C. elegans, thus making it suitable for conducting rapid experiments. Also noteworthy is the fact that between 60 to 80 percent of the 20,000 genes in the genome of C. elegans have similar origins to human genes. The genes are found consistently along the evolutionary paths, including those of both worms and humans.
“The good news is that this is a way of testing to show the medicinal effect. It is now testable. We have statistical evidence for the first time in C. elegans for a multi-compound drug,” said Dr. Luo. “Most [scientists] are not using whole organisms for screening herbs. This is simple and clean, it is a system to look at specific genes. Now we have to further validate the human relevancy.”
The Worm is the Word
In Frank Herbert’s science fiction Dune series, sandworms are given numerous titles such as the “Great Maker” and the “Worm who is God.” Virtually indestructible and with lifespans of potentially thousands of years, these giant sandworms help to produce the spice melange, the most essential and valuable commodity in the universe. Yet ironically, they also prevent easy harvesting, making the collecting of melange extremely hazardous and deadly.
Melange is a geriatric drug that gives the user an extended lifespan, along with greater vitality, and heightened awareness. Melange can also unlock prescience in some subjects, depending upon how much is taken and the consumer’s physiology. When prescience is achieved, interstellar travel is possible. However, the hardships of melange harvesting makes it very expensive. Moreover, it is highly addictive, and withdrawal is a fatal process.
Fortunately, the spice of C. elegans longevity has none of these dangers connected with it, and the worms are benevolent. While the prescience benefits of melange are a fantasy, it is worth noting that the SQDB formulation—which contains the spice cinnamon—enhanced the levels of some monoamines and their metabolites in the brains of aged mice, making them comparable to those of young mice in a prior study. So, if there is a rational basis for knowing things that you don’t immediately think you know, having higher levels of norepinepherine, serotonin and their metabolites can only help. And as we reported earlier in this article, cinnamon can tame the ulcer-producing effects of serotonin. Can it help to release its productivity-enhancing powers? Stay tuned.
- Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature 1993 Dec 2;366(6454):461-4.
- Kenyon CJ. The genetics of ageing. Nature 2010 Mar 25;464(7288):504-12.
- Yu YB, Dosanjh L, Lao L, Tan M, Shim BS, Luo Y. Cinnamomum cassia bark in two herbal formulas increases life span in Caenorhabditis elegans via insulin signaling and stress response pathways. PLoS ONE [online journal]. 2010;5(2):9339.
- Peterson DW, George RC, Scaramozzino F, LaPointe NE, Anderson RA, Graves DJ, Lew J. Cinnamon extract inhibits tau aggregation associated with Alzheimer’s disease in vitro. J Alzheimers Dis 2009;17(3):585-7.
- Tanaka S, Yoon YH, Fukui H, Tabata M, Akira T, Okano K, Iwai M, Iga Y, Yokoyama K. Antiulcerogenic compounds isolated from Chinese cinnamon. Planta Med 1989 Jun;55(3):245-8.
- Akira T, Tanaka S, Tabata M. Pharmacological studies on the antiulcerogenic activity of chinese cinnamon. Planta Med 1986 Dec;52(6):440-3.
- University of Maryland Baltimore (2010, April 9). Tiny worms employed to unlock keys to herbal medicines. ScienceDaily. Retrieved May 4, 2010, from http://www.sciencedaily.com/releases/2010/03/100329082009.htm.
- Tsunemi A, Utsuyama M, Seidler BK, Kobayashi S, Hirokawa K. Age-related decline of brain monoamines in mice is reversed to young level by Japanese herbal medicine. Neurochem Res 2005 Jan;30(1):75-81. Erratum in: Neurochem Res 2005 Feb;30(2):289.
Will Block is the publisher and editorial director of Life Enhancement magazine.