Dimitar Marinov, Ph.D.
Dimitar Marinov, Ph.D.Researchers interested in investigating peptides for anti-aging and longevity have come to the perfect place.
Our peptide experts have compiled relevant research findings that touch on the most common age-related concerns, identifying which peptides might work best to mitigate them.
Research peptides like epithalon, GHK-Cu and CJC-1295 are believed to offer benefits such as:
- Slowing down the aging process
- Reinforcing skin health and rejuvenation
- Protecting against age-related diseases
Continue reading to uncover the peptides that hold the greatest promise in anti-aging and longevity research, including our examination of their mechanisms, effects, and safety.
To kick things off, we introduce our top three recommended peptides for anti-aging and longevity research.
Top 3 Peptides For Longevity
Here are the top three peptides for research into anti-aging and longevity based on the available scientific information and data.
1. GHK-Cu
GHK-Cu, or copper peptide, is found in body fluids, peaking in concentration in humans between the ages 20-25. GHK-Cu shows skin-related benefits by stimulating collagen and glycosaminoglycan turnover, signaling tissue repair, and reducing oxidative stress [1, 2, 3]. Studies suggest that the peptide may reduce wrinkle volume by about 50% within eight weeks [4].
2. Epithalon
Epithalon is a tetrapeptide isolated from pineal gland extracts that upregulates telomerase activity, promoting telomere length and cellular longevity. Clinical trials have shown its potential in reducing mortality, decelerating cardiovascular disease progression, and other health benefits [5, 6, 7, 8, 9].
3. Argireline
Argireline is the brand name for acetyl hexapeptide-3, a peptide designed to target skin wrinkles by blocking neurotransmitter release, mimicking the effects of Botox. Yet, Argireline appears to be effective even when applied topically. In-depth trials have demonstrated its anti-wrinkle effectiveness, with one study showing a 48.9% wrinkle depth reduction after four weeks of application of a 10% Argireline cream [10, 11, 12, 13].
What Are Research Peptides?
Peptides are organic molecules found in all living organisms. They also can be synthesized for therapeutic or research purposes.
Generally speaking, peptides are sequences of amino acids connected by peptide bonds. Most peptides have a linear structure, but some can also be cyclical or branched.
Regardless, each peptide is made of between two and approximately 50 amino acids, the sequence of which determines the properties of the given peptide [14].
Peptides are sometimes referred to as “small proteins,” whereas proteins consisting of hundreds or even thousands of amino acids are simply called proteins, rather than peptides.
Vital for many essential physiological processes, such as hormonal signaling, cell regulation, neurotransmission, and healing, peptides are now at the forefront of clinical research.
As of writing, the United States Food and Drug Administration (FDA) has approved about 60 peptide compounds for applications such as [15, 16]:
- weight loss
- lipodystrophy
- complex oncotherapy
- type 2 diabetes
- low libido in women
- pain management
- short-bowel syndrome
How Do Peptides Work For Anti-Aging?
Peptides for anti-aging and longevity are a diverse group of compounds, each appearing to exert effects through a variety of mechanisms.
For simplicity, the terms “anti-aging” and “longevity” will be employed throughout this article, with the caveat that the mechanisms of action of the so-called anti-aging peptides do not necessarily involve the aging process per se, but rather manifestations of aging.
As an example, in the case of skin, outward manifestations of aging like wrinkles can be affected through interventions involving synthesis and processing of various types of collagen and elastic fibers without the cells producing those fibers becoming more youthful.
Some peptides such as GHK-Cu have been suggested to work via multiple mechanisms, including [17]:
- Activation of the Ubiquitin/Proteasome System (UPS): GHK-Cu enhances the UPS, which removes damaged proteins and can help decelerate aging.
- Activation of DNA repair genes: As DNA damage accumulates with age, GHK-Cu's ability to reactivate DNA repair genes can reduce the harmful effects of aging.
- Antioxidant gene activation: GHK-Cu works against free radicals and toxic products linked to aging-related diseases.
- Suppression of Insulin and insulin-like genes: High insulin and insulin-like protein levels can reduce lifespan. GHK-Cu suppresses these genes, potentially promoting longevity.
- Tissue repair via the TGF Superfamily: GHK-Cu facilitates general tissue repair by activating the TGF Superfamily—a group of proteins involved in repairing damage to organs, skin, and other tissues.
- Signaling the repair of connective tissues, including the skin's derma: The GHK amino acid sequence is embedded within the alpha 2(I) chain of type I collagen—a primary structural protein in the skin which in the event of injury is enzymatically broken down to GHK. The presence of GHK triggers a cascade of repair processes.
Other peptides like epithalon have been linked to extended lifespan in various laboratory models, and the peptide is suggested to work via:
- Suppression of CCl11 and HMGB1 genes, with the effect of increasing the lifespan of human somatic cells [18].
- Upregulation of telomerase activity and elongation of telomeres, with the effect of delaying aging processes in various cells and tissues [6, 7].
- Reducing the expression of apoptosis-inducing molecules like caspase-3 and, consequently, MMP-9 (matrix metalloproteinase-9) below the level observed in young cell cultures [19].
Lastly, peptide compounds like Argireline, SNAP-8, and SYN-AKE work by minimizing the signs of aging, such as wrinkles, without actually increasing the lifespan or renewal of cells. They work primarily by inhibiting muscle contractions, leading to reduced wrinkle depth and size [10, 11].
Do Anti-Aging Peptides *Actually* Work?
Research suggests that peptides may effectively provide anti-aging benefits for different tissues. Below, we outline two of the most notable examples:
- Skin: The most notable effects of anti-aging peptides have been observed in relation to the skin. For example, a trial in 40 middle-aged women reported that topical GHK-Cu administered twice daily led to 55.8% reduced wrinkle volume and 32.8% reduced wrinkle depth within 8 weeks [4]. Other peptides that work by upregulating the production of growth hormone (GH) report beneficial effects for the skin of elderly individuals, such as increased collagen production and improved skin thickness [20].
- Cardiopulmonary system: An epithalon study in 266 participants, which included a 6-8 year follow-up period, reported a significant reduction in clinical manifestations of ischemic heart disease, hypertension, and acute respiratory disease incidence. Most notably, the mortality rate in the epithalon-treated group decreased by 1.6-1.8x compared to controls [8]. Similar trials with up to 15 years of follow-up report decelerated aging of the cardiovascular system following epithalon administration [21].
Best Peptides For Anti-Aging, Longevity, and More
Below, we break down the five most notable research peptides for anti-aging and longevity, including their corresponding mechanism and benefits.
GHK-Cu
GHK-Cu (glycyl-l-histidyl-l-lysine-copper), aka copper peptide, is an endogenously produced peptide that researchers discovered when plasma from younger subjects was observed to facilitate protein synthesis in hepatocytes (liver cells) cultivated from older individuals [2].
Eventually, the research team determined that the factor stimulating these anti-aging effects was the tripeptide GHK, which has a high affinity to copper ions and readily binds to them, forming GHK-Cu. The peptide was eventually found in all bodily fluids (blood, urine, saliva, etc.), observing that its levels appeared to be at their highest at the ages of 20-25, after which they began to decline [1].
GHK-Cu appears to have notable anti-aging effects on the skin, which may be exerted via:
- Stimulating the turnover of collagen and glycosaminoglycans: These compounds are the main extracellular components of tissues such as the skin, and GHK-Cu has been suggested to increase both their breakdown and synthesis. As a result, the old matrix components get replaced with new ones [1, 2].
- Signaling for tissue repair: GHK is a tripeptide released upon the enzymatic breakdown of the alpha 2(I) chain of type I collagen, a major component of the connective tissues in bone, the cornea, dermis, and tendons. This enzymatic breakdown occurs in injuries, releasing GHK as a repair signal [2].
- Reducing oxidative stress: GHK-CU may protect against reactive carbonyl species, prevent protein glycation, and reduce the photoaging effects of ultraviolet (UV)-radiation [3].
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Epithalon
Epithalon (also known as Epitalon or AEDG peptide) is a tetrapeptide (Ala-Glu-Asp-Gly) that is isolated from a crude polypeptide called epithalamin, which is extracted from the pineal gland.
It was discovered in the 1980s by a research team led by Professor Vladimir Khavinson of the St. Petersburg Institute of Bioregulation and Gerontology [5].
The peptide appears to work by upregulating telomerase activity, which helps to maintain and extend the length of telomeres, the protective caps at the end of chromosomes. Longer telomeres are associated with increased longevity of certain cell types, leading to the hypothesis that elongation of telomeres by upregulating telomerase throughout the body can slow or reverse the aging process [6, 7, 8, 9].
While compelling evidence for this idea exists, it has not yet been substantiated clinically.
One study in 79 coronary patients, involving a total of six epithalon courses (five 10mg injections each) over three years and a 15 year follow-up, reported decelerated progression of cardiovascular disease, better physical endurance, normalized circadian rhythm, and improved metabolism compared to controls [21].
In addition, epithalon has also been tested in preclinical studies for its potential in:
- Preventing tumor formation [22]
- Reducing oxidative stress [23]
- Improving endocrine and immune health [24]
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Argireline
Argireline is the brand name for the peptide acetyl hexapeptide-3, alternatively known as acetyl hexapeptide-8. This anti-aging peptide works primarily by targeting signs of aging on the skin [10].
It is specifically designed from the N-terminal end of a protein called SNAP-25 (synaptosome-associated protein 25kDa) to target and reduce visible skin wrinkles.
SNAP-25 is a protein involved in the process of neurotransmitter release in neurons. It's a component of the SNARE complex, which facilitates vesicle fusion and the subsequent release of neurotransmitters at synapses [11].
Argireline works by blocking this release of neurotransmitters responsible for facial muscle contractions, a process similar to that of the popular botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and injected as “Botox.” However, the key difference is that Argireline offers these benefits when applied as a topical cream [12].
Two notable trials have compared the anti-wrinkle effectiveness of Argireline against placebo, including:
- A study in 60 female participants reported a 48.9% reduction in wrinkle depth after four weeks of application of a 10% Argireline cream, compared to a 0% reduction in wrinkle depth with placebo [13].
- Another study reported a 30% reduction in wrinkle depth within 30 days of daily application of a 10% Argireline cream, compared to a 10% reduction in wrinkle depth with placebo [25].
CJC-1295
CJC-1295, aka modified GRF 1-29, is a peptide analog of growth hormone-releasing hormone (GHRH) that was developed to treat abnormal fat distribution in HIV/AIDS patients.
It comprises the first 29 amino acids of GHRH, which represent the shortest GHRH sequence required for pituitary receptor binding and GH release [26].
In addition, CJC-1295 substitutes four of the original 29 amino acids substituted to enhance half-life from 10 to 30 minutes. It is also commonly modified with a drug affinity complex (DAC) that facilitates binding to plasma proteins and extends regular CJC-1295’s half-life to eight days [27, 28, 29].
By increasing GH levels, CJC-1295 is thought to facilitate a wide range of benefits, including:
- Abdominal fat loss
- Increased lean mass
- Improved physical performance
In addition, the peptide may facilitate increased cell proliferation and collagen production in the skin, which reduces the signs of aging.
This is further suggested by trials on partially modified versions of GRF 1-29, which suggest that 16 weeks of administration at 10mcg/daily can increase skin thickness in both male and female subjects. This effect is likely due to the increased GH levels enhancing fibroblast proliferation and function, leading to better collagen production [20, 30].
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Peptides Side Effects and Safety
Overall, peptides for anti-aging and longevity have favorable safety profiles. Yet, none of the aforementioned peptides are approved for human use, so researchers must exercise caution before incorporating them into their research.
Preclinical and clinical research into both GHK-Cu and epithalon suggests that the peptides are well-tolerated without any notable side effects [2, 24].
Studies into CJC-1295 have reported mild to moderate adverse reactions, such as [31, 32]:
- Nausea
- Abdominal pain
- Facial flushing
- Increased heart rate
- Headaches
- Diarrhea
In addition, the peptide may also lead to side effects like water retention and insulin resistance, which are related to its effect of increasing GH levels.
Injectable peptides such as GHK-Cu, epithalon, and CJC-1295 can also lead to local reactions at the injection site, such as:
- Bleeding
- Swelling
- Induration
- Inflammation
- Pain
According to the available research, the transdermal application of peptides such as topical GHK-Cu and Argireline is associated with a favorable safety outlook as these formulations do not penetrate deep within the skin to reach systemic circulation [4, 10, 25, 33, 34].
Cosmetic Peptides | Cure For Wrinkles?
As mentioned, peptides such as GHK-Cu may be highly effective for reducing signs of skin aging, as studies report up to 55.8% reduced wrinkle volume and 32.8% reduced wrinkle depth within eight weeks of daily application [4].
Studies with Argireline also report 30-50% wrinkle depth reduction with a 10% Argireline emulsion applied twice daily for one month compared to 0-10% improvement on the control side [13, 25].
Several other peptides that may effectively reduce wrinkle depth include:
- Syn-Coll, aka palmitoyl tripeptide-5, is a synthetic peptide that can boost the skin's collagen production by activating the transforming growth factor beta (TGFB). In addition, Syn-Coll has the potential to restrict matrix metalloproteinases (MMPs) like MMP1 and MMP3, which are known to break down collagen. By increasing collagen in the dermis, Syn-Coll has been noted to diminish the appearance of fine lines and wrinkles [10, 33, 35].
- SNAP-8, aka acetyl octapeptide-3 or acetyl octapeptide-1, is another inhibitor of SNAP-25 that blocks the release of acetylcholine, thereby limiting facial muscle contractions. Studies suggest that SNAP-8 can reduce wrinkle depth by up to 65%, with an average reduction of 35% [10].
- SYN-AKE, aka tripeptide-3, is a peptide developed by Swiss scientists to replicate the impact of waglerin-1, a compound found in temple viper venom. It temporarily obstructs the muscular blocks acetylcholine receptors, preventing facial muscle contractions. Studies indicate that a 28-day trial of SYN-AKE can decrease wrinkle visibility by as much as 52% [10, 36, 37].
Can Peptides Reverse Aging?
Peptides have emerged as promising agents in the quest to counteract age-related concerns, with various studies highlighting their potential in skin rejuvenation, cardiopulmonary system improvement, and even lifespan extension in laboratory models.
Particularly, peptides like GHK-Cu, epithalon, and Argireline have shown significant potential in reversing many of the signs of aging and even slowing disease progression.
However, while peptides certainly hold potential in the anti-aging sphere, they may not be the proverbial fountain of youth that completely reverses the aging process.
Furthermore, many of the peptides mentioned above require more comprehensive and rigorous research by scientists to fully uncover their potential.
At this time, peptides such as GHK-Cu, epithalon, Argireline, and CJC-1295 are available online strictly to qualified researchers who aim to incorporate them into their studies.
Peptides and Anti-Aging | Verdict
Some of the most actively researched peptides for anti-aging and longevity are GHK-Cu, epithalon, CJC-1295, and Argireline.
These compounds each showcase anti-aging and longevity potential through various mechanisms, from interacting with DNA and reducing oxidative stress to prolonging cellular lifespan and reducing visible wrinkles.
However, it's crucial to note that while these peptides exhibit promising results, they are still under intense scientific scrutiny, and comprehensive clinical data remain to be elucidated.
Qualified professionals looking to delve deeper into the world of anti-aging peptides are encouraged to visit our top peptide vendor for more information.
David Warmflash, M.D.