Peptide Sciences Blog
Follistatin 344 (and 315)
Follistatin, also called activin-binding protein, is found in nearly all tissues of vertebrate animals. Its primary function is to neutralize members of the TGF-β family, which play fundamental roles in everything from growth and development to energy homeostasis and immune system regulation. In particular, follistatin interacts with activin, which plays an important part in cell proliferation and cell death as well as in the immune response as it applies to wound repair1,2.
Follistatin 344 and 315 are engineered analogues of naturally occurring follistatin. Both are created by alternative splicing of the follistatin mRNA transcript. Scientific research in non-human primates as well as in mice have indicated that both molecules are capable of improving muscle growth by antagonizing myostatin (a member of the TGF-β family).
Follistatin 344 Research Studies
The first evidence that follistatin could enhance muscle growth came from studies conducted in mice in 2001. These studies found that myostatin, a known negative regulator of skeletal muscle growth, interacted with activin type II receptors found on muscle cells. Follistatin 344 interacts with these same receptors and is a competitive antagonist to myostatin. By blocking myostatin’s ability to bind to the activin receptors on muscle cells, follistatin 344 can allow for massive increases in muscle mass3.
Scientists are speculating on a number of ways that follistatin may be put to clinical use for muscle growth in the future. Research in mice from 2009 has indicated that follistatin might be useful in the disease spinal muscular atrophy (SMA). In SMA, there is a loss of function mutation that causes death of spinal motor neurons. When these nerves die, the muscles that they connect to atrophy as well. Research shows that follistatin not only preserves muscle tissue in mice with SMA, but that it also helps to preserve spinal motor neurons by creating a positive feedback loop. In fact, the mice in the study group lived 30% longer than mice who were not given Follistatin because of enhanced muscle and nerve cell survival4.
Another way in which the muscle-building benefits of follistatin may be put to good use in the future is in the treatment of muscular dystrophy and inclusion body myositis. In both diseases, muscle wasting leaves people too frail to walk or even breathe on their own. Even modest improvements in muscle mass and function would be life-changing for those suffering from these diseases5,6.
Epithalon and Skin Rejuvenation
Skin rejuvenation is often associated with wrinkles and lines, but the truth runs deeper than wrinkles. Skin becomes more fragile and thus more prone to damage as it ages. Damage to the skin compromises its protective barrier function and can increase risk of infection. Research into ways to strengthen skin can not only make skin look younger, but can protect people from serious medical conditions. Thus far, most skin rejuvenation research has focused on collagen and other large skin proteins. New research, however, suggests that short peptide molecules, like epithalon, may hold more promise in preserving and even rejuvenating skin.
Epithalon (a.k.a. epitalon), is a short (just four amino acids long) peptide that has been demonstrated to have anti-aging and anti-cancer properties in rodent studies. Because epithalon is so short, it can penetrate the cell membrane, without the aid of transporters, and make its way to the nucleus of cells. This is important because, once in the nucleus, epithalon can affect the regulation of genes, activating some and deactivating others to cause cell-wide changes1.
Previous research has indicated that epithalon can stimulate immune system function that has been lost due to natural aging. Investigation of the mechanism of this action uncovered the ability of the Ala-Glu-Asp-Gly peptide chain (Epithalon) to interact with the promoter region of the interferon gamma gene. By promoting the production of interferon gamma, a key immune regulator, epithalon is able to boost functioning in T-cells and thus overall immunity and well being1,2.
The idea that short peptides might be able to affect DNA-level processes has caused a boom in the investigation and research of epithalon and other short peptides in animal models. Those investigations have led to the understanding that epithalon can impact skin aging by activating cellular repair processes, which often go dormant as we age.
GHK-Cu is a naturally occurring peptide, made of the three amino acids Glycine-Histidine-Lysine, that is complexed with a copper molecule. It was first isolated from human plasma (a part of blood), but can also be found in saliva and urine. It has been linked to skin and tissue healing as well as to immune function and antioxidant generation. Like many natural anti-aging compounds, tissue levels of GHK-Cu tend to drop as humans age, from a high of about 200 micrograms per milliliter at age 20 to a low of 80 micrograms per milliliter by age 601.
GHK-Cu and Skin Healing
About a decade ago, research studies revealed that GHK-Cu is involved in wound healing and in the regulation of scar formation. The list of processes that research has shown GHK-Cu to be involved in includes
- Attracting cells that are involved in the repair process,
- Suppressing free radicals,
- Reducing inflammation by boosting levels of key anti-inflammatory molecules,
- Increasing protein synthesis, and
- Increasing fibroblast growth and differentiation1.
Research from 2014 suggests that GHK-Cu may play an important role in regulating levels of transforming growth factor-β and insulin-like growth factor-2. By increasing levels of TGF-β and decreasing levels of IGF-2, GHK-Cu is able to improve skin healing while reducing the formation of hypertrophic scars2.
Controlled studies of GHK-Cu and aging skin in animals indicate that the peptide tightens skin, improves firmness, boosts elasticity, reduces fine lines and wrinkles, and helps to resolve photo damage. More recent research has also indicated that GHK-Cu can protect the liver from toxins, boost bone growth, and protect gastrointestinal tissue from ulcer formation. Now, it turns out, GHK-Cu also plays a role in protecting against microbial invaders.
AICAR is an AMP-kinase activator widely used in animal research to investigate energy homeostasis and the regulation of metabolism. Studies have found that AICAR can regulate insulin receptors and change muscle cell function, which has led to investigations into its use for the management of diabetes. The molecule has also been found to have anti-cancer properties, slowing the growth of cancer cells both in vivo and in mouse models. It has additionally been used, in the past, to protect heart muscle during surgery1.
What Is AICAR?
AICAR is short for 5-aminoimidazole--4-carboxamide ribonucleoside. It is also called acadesine. It is actually a naturally occurring molecule, acting as an intermediate in the production of other nucleosides. Because it is an intermediate, AICAR is not found in substantial quantities in living organisms.
What makes AICAR so interesting to the research community is that it can penetrate cell walls. Unlike many compounds, it can pass through a cell wall without difficulty and without being altered. That means it is easy to get AICAR to the interior of the cell where it can act to regulate metabolism, cell growth, and cell death.
Peptides: What Are They?
Peptides are biological materials that are made from building blocks called amino acids. Animals get most of their amino acids from the foods they eat. Different cells then assemble these amino acids into long chains called peptides or proteins. As the chains grown in length, they are able to fold back on themselves. As it turns out, certain amino acids can interact with one another when peptide chains fold. This results in the folds being locked into place, under normal physiologic conditions, which gives the peptide chain a three-dimensional structure. The length of the peptide chain as well as the order of the amino acids in it determines how the peptide folds and thus its ultimate three dimensional structure.
Receptors, special biological machines to which proteins can bind, will only accept proteins that have the right order of amino acids and the right three dimensional shape. By varying these two properties, it is possible to create proteins that have specific and very diverse functions. Research studies have shown that the peptide that binds to receptors in the heart, for instance, may not interact at all with receptors in the stomach or lungs. This allows for very specific signals to be sent from one region of the body to another, which allows for coordinated actions such as immune function, carbohydrate metabolism, and so forth.
There is no formal definition for what makes a peptide “small,” but they often don’t have much in the way of three-dimensional structure. They may have a fold or two, but that is about it. These peptides rely more on their amino acid sequence than their 3-D structure for signaling. Even a small change in the order of the amino acids of a small peptide (or even the number) can make a huge difference in terms of the receptors that it can bind to. Sometimes, a change of just a single amino acid is enough to completely alter the function of a small peptide.
In the past, most of the research focus was on larger peptides and massive proteins. This was because most scientists thought that biologically active proteins were large. It was also thought that the best way to develop therapeutics was to exactly mimic existing proteins. This approach, however, isn’t entirely accurate.
New research is indicating that small peptides are not only easier to make; they can also have a wide range of biological activity. It is no longer thought that mimicking naturally occurring proteins is the best way to develop therapeutics. Science has now shifted its focus to small peptides and their potential. This shift makes sense given that small peptides have been shown to have applications ranging from antibiotics and heart medications to preventative solutions for diseases like diabetes. They have even been shown to have anti-aging effects in animal models.
The Future of Small Peptides
It is clear that the future of medicine will be rife with small peptides. They won’t be the only therapeutics available, but they will continue to make up a larger and larger percentage of the substances we use to promote health. Most importantly, small peptides can be custom-made to fight off disease and preserve health. They are less complicated to synthesize and produce and what we learn from early research trials will certainly inform us moving forward. Within a decade or two, small peptides will be as common in the medical field as antibiotics and vaccines are today.
BPC 157 and Healing
BPC 157 is a part of a naturally occurring protein known as body protection compound (BPC). BPC was first isolated from gastric (stomach) juice, but has also been found in other locations, such as the skin and liver. Previous research in animal test subjects has indicated that BPC 157 and BPC both promote healing. New animal research is starting to shed some light on just how they do that.
Fibroblast Outgrowth and Migration
Fibroblasts are motile (move about) cells found in most connective tissue (bones, tendons, muscle, gastric mucosa, skin, etc.). When damage to tissue occurs, fibroblasts migrate to the site of injury in order to begin the process of repair. They also divide and reproduce (outgrowth) to increase the number of fibroblasts available for tissue repair.
In in vitro studies reveal that migration of fibroblasts is directly affected by BPC 157 concentrations. Where BPC 157 levels are the highest, more fibroblasts can be found.
Evidence shows that BPC 157 is not just an attractant, but that it causes fibroblasts to migrate nearly 2.5 times faster than normal. Not only do the cells migrate in response to BPC 157 levels, they reproduce in response to them as well. Fibroblast outgrowth is approximately three times higher in the presence of BPC 157 .
Cell Survival and BPC 157
In vitro experiments indicate that fibroblasts survive for longer in the presence of BPC 157. Fibroblasts survive about 1.5 times longer when BPC 157 is present . What is more, those cells tend to be healthier and more active and thus more capable of carrying out their repair roles.
The Net Effect
By encouraging fibroblast migration, enhancing fibroblast survival, and increasing the speed at which fibroblasts are able to reach a site of injury, BPC 157 increases rates of tissue repair by several orders of magnitude. All of this is achieved by simply stimulating natural healing processes. BPC 157 can best be thought of as boosting the function of the body's natural repair mechanisms.
 C.-H. Chang, W.-C. Tsai, M.-S. Lin, Y.-H. Hsu, and J.-H. S. Pang, "The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration," J. Appl. Physiol., vol. 110, no. 3, pp. 774-780, Mar. 2011.
 B. Bódis, O. Karádi, P. Németh, C. Dohoczky, M. Kolega, and G. Mózsik, "Evidence for direct cellular protective effect of PL-10 substances (synthesized parts of body protection compound, BPC) and their specificity to gastric mucosal cells," Life Sci., vol. 61, no. 16, p. PL 243-248, 1997.
TB-500 is also known as thymosin beta 4 (TB4). Thymosin Beta 4 has been found, in animal models, to play a central role in controlling the structure of cells. By improving cell structure, TB-500 is thought to aid in wound healing, improve cell responses to stress, and even help cells to live longer. Scientific animal research studies have shown that TB-500's role in regulating cell structure may eventually make it a leading therapeutic in wound healing, blood vessel repair, and even ocular (eye) repair.
Fifteen years ago, orexins were identified as central regulators of energy homeostasis. Research indicates that orexins are key modulators of the sleep-wake cycle and that these neuropeptides also affect feelings of satiety and hunger. Given their role in energy homeostasis, it was hypothesized that orexin levels are likely regulated, at least in part, by the growth hormone axis. Recent research supports this fact and suggests that growth hormone releasing hormone analogues, such as sermorelin, may be effective in treating conditions in which orexin release is dysfunctional (e.g. narcolepsy) .
Epithalon, also known as Epitalon is a synthetic peptide analog of epithalamin, a protein found in the pineal gland of mammals and of interest for its anti-aging properties. Past research studies have demonstrated that epithalamin can increase maximum life span in animals, decrease levels of free radicals, and alter catalase activity to prevent tissue damage . Epithalamin has been shown to decrease mortality by 52% in fruit flies, by 52% in normal rats, and by 27% in mice prone to certain types of cancer and cardiovascular disease .
Epithalon has similar effects to epithalamin in mice and rats. It has also shown promise as an anti-cancer agent, reducing spontaneous mammary tumors in mice prone to them and reducing incidence of intestinal tumors in rodents. How does it achieve these effects?
It is has been known for some time that leptin regulates satiety, but the exact mechanism of regulation has remained elusive. Research has recently revealed that leptin and melanocortins affect the same brain regions associated with hunger and metabolism. This finding has led to new insights into both leptin physiology and the effects of melanocortin analogues like melanotan-2 (MT-2).
The Role of Leptin in Hunger
Leptin, which is made by fat cells, controls both food intake and energy expenditure. A large majority of its effects are mediated through proopiomelanocortin (POMC) neurons in the central nervous system. By stimulating POMC neurons, leptin creates feelings of fullness. In some individuals, a decreased sensitivity of POMC neurons to leptin has been linked to an inability to detect satiety.
A peptide is nothing more than a string of amino acids that is similar to, but not identical to, a protein. To understand what a peptide is and how it differs from a protein, it is necessary to first understand what an amino acid is.
What Are Amino Acids?
Amino acids are biologically important molecules, but not all of them are used by living organisms. In fact, the human body requires only 20 different amino acids to function (the case for almost all living things), even though nearly 500 have been identified in the universe so far. Amino acids have two specific chemical structures, called amine and carboxylic acid groups, at opposite ends. These structures endow amino acids with a common set of functions and define how they interact with one another and with other molecules.
BPC 157 is a partial form of the protein known as body protection compound (BPC). BPC is a natural component within the body and has been found, in experiments on animals, to promote healing. BPC is not just active in intestinal repair and healing, but appears to produce similar effects in a number of tissues. Scientific studies based on animal test subjects has shown that its healing actions are at least partially linked to growth hormone (GH).
Research has shown that when it comes to brain health, there are few drugs, supplements, or diets that make much difference. Unfortunately, the brain has remained a mystery to medical science and thus efforts to determine how to keep the brain healthy have been hindered. Science can tell us only that regular exercise and a relatively meat-free diet are associated with long-term brain health. There may, however, be some new evidence regarding thymosin beta 4 (also known as TB-4, or TB-500) and its impact on neural health.
TB-500 (TB-4) is a naturally occurring peptide that is known to produce a vast array of healing and regenerative effects. It appears to promote everything from bone remodeling and growth after fracture to healing of heart muscle after a myocardial infarction (heart attack). Recent research in rats now suggests that TB-500 (TB-4) may improve neurological outcomes after stroke or brain damage.
IGF1 LR3 (insulin-like growth factor-1 Long R3) is a non-glycosylated, recombinant polypeptide chain made up of 83 amino acids. IGF1 LR3 is the recombinant form of human IGF-1, and as such it contains the entire native amino acid sequence but with two major modifications: substitution of arginine (abbreviated R or arg) at position 3 with glutamic acid (abbreviated E or Glu) hence the label R3; and the extension of the N-terminus of the native sequence by a 13 amino-acid peptide hence the label long. The native form of a polypeptide refers to the naturally occurring amino acid sequence and the resultant conformational structure. The molecular weight of IGF1 LR3 as measured by Mass Spectrometry is 9.116 kD (kiloDaltons). A specifically designed protein expression system is utilized in the production of IGF1 LR3 in Escherichia Coli. Thereafter, chromatographic techniques are used to correctly fold and purify the IGF1 LR3 to the highly-active and functional IGF1 LR3 that can bind to human IGF-1R (insulin-like growth factor-1 receptor).
Thymosin Alpha-1 is a biologically active peptide derived from prothymosin-alpha. Current hypotheses consider Thymosin Alpha-1 to be the main constituent of Thymosin Fraction-5, and as such it is considered to be the active component that restores the immune function in both athymic animals and animals with dysfunctional thymus glands. Thymosin Alpha-1 was among the first peptide isolates of Thymosin Fraction-5 to be sequenced and thereafter synthetically synthesized.
In humans, the PTMA gene encodes prothymosin-alpha, a 113 amino-acid polypeptide. Thymosin Alpha-1 is a 28 amino-acid fragment of prothymosin-alpha, and research has shown that this fragment derivative enhances the cell-mediated immune component of the human immune system. Its immune actions have enabled it to be used for treating viral infections such as Hepatitis B and Hepatitis C. It has also been incorporated into vaccines as an immune booster. Clinical studies have also shown that Thymosin Alpha-1 can be used to manage neoplasias since they upregulate cytotoxic T-cells which are involved in immune surveillance.