Best Peptides for Anti-Aging Research

Anti-aging research has hit its stride in the last decade with advancements coming at an ever-faster pace. Recently, at Kyoto University in Japan, biologist Shinya Yamanaka has shared the Nobel Prize in medicine for work he did into how peptides can be used to reprogram adult stem cells to reduce the effects of aging. The research revealed that a protein cocktail is able to turn back the clock in mouse models, restoring the epigenomes of the mice to a more youthful state and reducing inflammation, musculoskeletal dysfunction, cognitive decline, and more[1].

The advances made by Dr. Yamanaka come as no surprise to experienced anti-aging researchers because the trend has been toward more complex interventions using multiple peptides and approaches. According to Harvard’s David Sinclair, a founding member of the Paul F. Glenn Center for the Biology of Aging. According to Dr. Sinclair, the field has advanced during his career from extending the lives of relatively simple organisms like yeast and worms to being able to reverse aging in complex organisms like mice and non-human primates. Much of that progress has come from combining various techniques and layering knowledge to gain ever more sophisticated control of cellular aging. While Dr. Sinclair’s goal has primarily been to slow the onset of certain diseases associated with age, he points out that there is little difference between slowing disease onset and slowing aging. In fact, he points out that slowing the onset of heart disease, something that is commonly achieved in medicine today, is just an early form of slowing the aging process. Stem cell research and anti-aging proteins are just the next step on the path toward slowing the onset of aging and, eventually, maybe even halting aging altogether.

Peptides and Aging

At the forefront of current anti-aging research are techniques designed to reverse epigenetic changes in DNA. Epigenetic changes refer to changes in DNA expression patterns and not to changes in the DNA sequence itself. Research shows that, as part of the aging process, some genes are turned on and some are turned off. This leads to several the effects we associate with aging such as lower testosterone, lower growth hormone, changes in estrogen levels, alterations in wound healing, a decline immune function, changes in skin structure, alterations in learning and memory, and more.

The reversal of epigenetic changes has been shown in previous research to diminish or even reverse the effects of aging but has been difficult to achieve outside of cell culture. The discovery that peptides, particularly small peptides, can penetrate cell membranes and act as epigenetic signals has led to a rush to understand how these peptides can be useful both in isolation and in combination. Dr. Yamanaka’s research focused on the ability of certain peptides, in combination, to slow or reverse certain aspects of aging. There are a handful of peptides that have proved to be particularly interesting because of their widespread and obvious effects on aging in a variety of tissues. These peptides have helped to not only reverse the effects of aging in mouse models but have revealed some of the mechanisms by which aging occurs. Thus, these peptides, discussed below, have helped to advance the science a great deal. What is more, they are still offering insight to scientist who design careful trials to explore their function and mechanisms of action.

New Work on Epigenetics

Before discussing the best peptides for anti-aging research in detail, it is important to note that, in recent years, the role of epigenetics in aging has gained more attention. In particular, the role of a gene called WRN has garnered a great deal of interest. Research into a disease called Werner syndrome has revealed that a single mutation in a gene called WRN leads to premature aging. It appears that WRN plays an important role in the winding and unwinding of DNA, thus affecting DNA expression patterns. What came as news, however, was the discovery that WRN dysfunction is not limited to disease processes like Werner disease. In fact, WRN losses its function with time, causing alterations in DNA expression patterns, changes to telomere function, increases in mitochondrial dysfunction, and increases in oxidative stresses that lead to some of the signs of aging[2].

Source: Science.org

Scientists at the Salk Institute for Biological Studies suggest that even small problems with the WRN gene and the protein it produces could be contributory or even causative in diseases such as cancer, diabetes, and Alzheimer’s disease. Research is ongoing to understand how to influence WRN function, with scientists wondering what role this epigenetic control protein will play in future anti-aging research. These findings, however, helped to cement the idea that epigenetic changes are at the heart of many disease processes and the aging process itself. Altering the ability of a cell to access genes that code for antioxidants, reduce inflammation, or improve nutrient function must necessarily make all of these tasks more difficult and leads to accumulated cellular damage that eventually leads to senescence or even cell death.

Of course, alterations of DNA expression patterns are not the only way that peptides can slow or reverse aging. Some peptides work by directly restoring the balance of certain hormones, replenishing antioxidants, reducing inflammation, improving wound healing, or increasing protein synthesis. In fact, some peptides have been shown to do many or even all these things, including altering DNA expression patterns. The deeper science looks, the more complex the process of aging becomes. Peptides have been and will continue to be an important tool for exploring the biological mechanisms of aging and teasing apart their intricacies. Here is a look at some of the peptides that have advanced research the most and which continue to reveal the secrets of aging to researchers the world over.

Sermorelin

The king of all anti-aging peptides is sermorelin. According to Dr. Richard Walker, founder of the International Society for Applied Research in Aging, sermorelin is the closest that humanity has yet come to discovering the fountain of youth[3]. He says this primarily because sermorelin can directly reverse the decline of growth hormone that occurs as we age. Referred to as somatopause, lower levels of growth hormone can lead to several the problems we associate with aging such as difficulty maintaining weight, changes in bone and muscle strength, deteriorating cardiac and vascular health, changes in cognition, worsening immune system function, and changes in sleep patterns.

Sermorelin is a growth hormone releasing hormone analogue. It has been around for a very long time and has been the subject of extensive research. Studies show that sermorelin can restore growth hormone levels without altering the patterns by which growth hormone is naturally secreted. This results in a physiologically based boost in growth hormone levels that can improve wound healing, increase lean body mass, improve sleep, and even alter food preferences. Sermorelin boosts protein synthesis, restores growth hormone balance, and reduces inflammation. Recently, research has even suggested that sermorelin may alter patterns of DNA expression and that it has definitive effects on cognition and memory.

Ipamorelin

Ipamorelin is named similarly to sermorelin and though both peptides increase growth hormone levels, they do so by binding to different receptors. Ipamorelin is a growth hormone secretagogue receptor agonist and mimics the effects of naturally occurring ghrelin. Ipamorelin can produce profound spikes in growth hormone levels that have been shown to improve several physiological functions both acutely and over the long-term.

Research shows that ipamorelin can increase muscle growth, thwart diabetes, and improve bowel function. It is also a potent stimulator of bone growth and has been tested in clinical trials as a potential treatment of osteoporosis and other bone diseases, many of which are brought on or exacerbated by aging. By offsetting somatopause, ipamorelin helps to prevent changes associated with decreasing growth hormone. These include wrinkles, loss of strength, decreasing bone density, changes in cognition, and more.

Epithalon

Early research on Epithalon was performed using insects and revealed that the peptide can decrease mortality by up to 52% while extending life by as much as 27%. At first, it was thought that the entirety of Epithalon’s lifespan-extending action was a result of its antioxidant effects. The peptide is, after all, a potent eliminator of free radicals and thus helps to prevent protein and DNA damage. Further research, however, revealed that Epithalon turns up the activity of an enzyme called telomerase. Telomeres protect DNA from damage, but they get shorter with time. The enzyme telomerase is the only known enzyme to restore telomeres after they are shortened. Unfortunately, telomerase activity decreases as we age, at least in part due to epigenetic changes. When telomeres are shortened, signals are sent to cells telling them to stop dividing and reproducing. When enough cells get the signal to stop reproducing, tissue health begins to decline and eventually tissues fail. This slow degradation in tissue health is referred to as senescence and is a primary driver of the aging process. Epithalon helps to increase the activity of telomerase and thus protects DNA. This slows the onset of senescence, extending tissue health and extending lifespan.

GHK-Cu

GHK-Cu is a short peptide that binds to copper. As with many of the peptides discussed in this article, levels of GHK-Cu decrease with age, and this leads to tissue dysfunction and disease. Copper metabolism, though not often discussed in the medical setting, is actually an important component of nervous system health. Alterations in copper metabolism have been linked to several neurological conditions including Parkinson’s disease and Alzheimer’s disease. These diseases of aging as well as general cognitive decline cannot be reverse by GHK-Cu, but there is good evidence from mouse models to indicate that maintaining GHK-Cu levels can help to prevent cognitive decline in the first place. In other words, maintaining GHK-Cu levels helps to slow the march of time as it relates to neurological tissue.

Research also shows that GHK-Cu is a potent regulator of the epigenome, helping to control the expression of genes and thus the proteins that they code for. New research shows that the expression of as much as one third of human DNA is under the control of GHK-Cu to some extent. Research in mice demonstrates that the genes that GHK-Cu controls via epigenetic changes can reduce inflammation, increase tissue repair, and enhance natural processes that help to remove waste and toxic metabolic byproducts from cells.

Humanin

Humanin is a naturally occurring micro peptide that plays an important role in the function of mitochondria. Mitochondria produce most of the energy that our cells use to function, grow, and divide. Research shows that changes in mitochondrial function are a primary driver of multiple aging processes such as free radical production, apoptosis, and inflammation. Dysfunction in mitochondria is mediated via several pathways, one of which is Bcl2-associated X protein (BAX). BAX regulates the process of apoptosis, which is programmed cell death. When activated, this protein complex associates with mitochondria and essentially shuts them down to cause cell death. Humanin prevents this from happening and helps to protect cells from apoptosis. Research shows that this can protect several sensitive tissues such as neurons, cardiac tissue, and the retinas of the eyes. There is a great deal of research into using humanin to prevent deterioration of eyesight, something that is common with aging.

P21

P21 is a lesser-known nootropic that helps to stimulate the growth of neurons and extend their longevity. It is a derivative of naturally occurring ciliary neurotrophic factor (CNTF) but does not interact with the CNTF receptor. Research shows that P21 likely works by inhibiting antibodies from forming against CNTF to neutralize it. This leads to an effective increase in P21 levels and thus decreased neuron death. In mouse models, the primary effect of P21 has been on the hippocampus, which is critical to the formation of memories and to the exploration and learning that occurs in new environments. There is interest in using P21 to both stave off the cognitive decline of aging and to enhance learning. P21 is under active investigation as a potential preventative for Alzheimer’s disease.

MOTS-c

MOTS-c is a mitochondrial protein that has been shown to play critical roles in age-dependent physical decline as well as muscle homeostasis. Interestingly, MOTS-c is one of the peptides that is affected by exercise and may, in part, explain why exercise can increase longevity and fight off everything from dementia to bone disease. Interestingly, supplementation with MOTS-c appears to have many of the benefits of exercise even in mice that are lethargic and consume high levels of fat.

MOTS-c is one of the proteins activated by ketogenic diets, like the Atkin’s diet. Research shows that MOTS-c regulates insulin sensitivity, metabolic homeostasis, and the folate cycle. While the major focus of MOTS-c research has been on its ability to protect against insulin resistance and diabetes, there is good reason to think that the peptide is important in antioxidant pathways and maybe even has an impact on DNA expression patterns.

A Summary of Anti-Aging Peptide Research

Peptides can thwart the effects of aging through multiple mechanisms. Some peptides alter DNA expression patterns, some enhance hormone signaling, others reduce inflammation and boost antioxidant activity, and still others increase protein synthesis and help to maintain homeostasis. Though the peptides above are discussed in isolation, research is increasingly focusing on their use in combination. Combining the various mechanisms of action of these peptides (and others) appears to enhance anti-aging benefits. While there is a great deal of research still to be done, animal models are providing tantalizing foresight into how these peptides are leading us down the path toward a biological fountain of youth. Peptides hold the potential to not only extend our lifespans, but to extend and improve our health even as we live longer.