Mitochondria are more than just the energy centers of cells; they play a crucial role in aging, chronic illnesses, and metabolic function.
Within this domain, two mitochondrial-targeted peptides MOTS‑c and SS‑31 stand out for their distinct abilities to enhance cellular performance.
MOTS‑c is a peptide naturally encoded by mitochondrial DNA, while SS‑31 (also known as Elamipretide) is a synthesized compound designed to stabilise mitochondrial membranes.
Their differing modes of action; one signaling metabolic defenses, the other shielding structural integrity, make them compelling but distinct solutions for mitochondrial dysfunction in aging or disease.
MOTS‑c (short for mitochondrial open reading frame of the 12S rRNA‑c) is unique among peptides, as it is derived from mitochondrial DNA instead of nuclear DNA.
It serves as a metabolic regulator, enhancing fat use, improving glucose processing, and increasing insulin sensitivity.
Under metabolic stress, it migrates into the cell nucleus and adjusts gene activity linked to inflammation control, cellular repair and stress resilience.
Animal models have shown MOTS‑c’s potential in metabolic health and longevity.
In a notable study by Lee et al, elderly insulin-resistant mice received MOTS‑c for seven days, resulting in complete restoration of insulin sensitivity to levels comparable with younger mice showcasing its promise for human metabolic disorders, cardiovascular aging, and obesity treatment.
SS‑31, also marketed as Elamipretide, is a lab-created tetrapeptide (tiny protein made up of four amino acids) designed to directly protect mitochondria.
It binds with cardiolipin, an essential phospholipid in the inner mitochondrial membrane, which supports electron transport chain efficiency.
Through this binding, SS‑31 stabilises membrane structure, lowers reactive oxygen species (ROS), and ensures sustained ATP production.
SS‑31 has been evaluated in both preclinical and clinical settings for conditions rooted in mitochondrial damage, such as heart failure, kidney injury, inherited mitochondrial muscle disorders, and age-related macular degeneration.
In one animal study, SS‑31 reduced diet-induced inflammation in glomeruli by approximately 50%, suggesting a protective effect on kidney function during metabolic stress.
SS-31 has been proven to be a mitochondrial-targeted therapeutic agent worth exploring more in chronic and acute disease.
Mitochondria have far-reaching roles beyond energy production.
They are central to immune response, regulation of cell death, and nutrient metabolism.
When mitochondrial function deteriorates, it contributes to numerous diseases, including neurodegenerative disorders, cancer, diabetes, and cardiovascular conditions.
The discovery of small peptides like Humanin and MOTS‑c, encoded directly by mitochondrial DNA, revealed mitochondria’s role as signaling devices.
These peptides travel through the bloodstream, acting on metabolic pathways, inflammation, gene regulation, and cellular resilience.
Unlike many medications that address symptoms, mitochondrial peptides have the potential to address the fundamental causes of cellular decline.
Potential benefits include:
Though both MOTS-c and SS-31 support mitochondrial health, their differences in design, function, and medical application are profound.
It is essential to understand these differences so the right decision can be made regarding which mitochondrial peptide is more suitable for specific aspects of mitochondrial dysfunction, aging and metabolic imbalance.
MOTS‑c has primarily been explored for:
SS‑31 has mainly been studied for:
SS-31 targets mitochondria directly and is therefore more applicable in tissue-specific diseases involving mitochondrial dysfunction.
MOTS‑c, being endogenous, appears well-tolerated in animal studies with minimal immune response.
SS‑31 has undergone several human clinical trials and thus shows a favorable short-term safety profile; long-term studies are still ongoing.
MOTS‑c is a 16-amino-acid peptide that works hormonally and is typically injected subcutaneously several times per week.
This allows for more flexible dosing schedules under experimental conditions
SS‑31 is a small, cell-permeable tetrapeptide with a shorter half-life, often requiring daily injections for sustained mitochondrial targeting.
SS‑31 has advanced through Phase 2 and 3 clinical trials.
SS-31 primarily targets mitochondrial diseases, age-related macular degeneration (AMD) and heart failure.
It has received orphan drug status designations for conditions such as Friedreich ataxia and Duchenne muscular dystrophy.
However, it has not received FDA approval for widespread use.
MOTS‑c remains in the preclinical and early clinical trial phase, with promising data, but no regulatory approval as of yet.
What is the main difference between MOTS‑c and SS‑31?
MOTS‑c is a peptide naturally produced by mitochondria that regulates metabolism and stress responses. SS‑31 is a synthetically engineered peptide that directly stabilizes mitochondrial membranes to preserve energy function and reduce oxidative damage.
Which peptide is better for improving mitochondrial function?
The answer depends on your objective. MOTS‑c supports long-term metabolic equilibrium and resilience, making it ideal for chronic conditions. SS‑31 provides immediate support to mitochondria, making it well-suited for acute or targeted mitochondrial deficits.
Which peptide, MOTS-c or SS-31, is best suited for me?
MOTS‑c is best suited for metabolic and age-related health decline, while SS‑31 is better for acute, organ-specific mitochondrial dysfunction; such as heart or kidney injury, retinal degeneration, and inherited mitochondrial diseases.
Is one peptide more natural or safer than the other?
MOTS‑c is naturally synthesized by the body, making it inherently compatible and unlikely to provoke an immune response. SS‑31, although synthetic, has shown solid short-term safety in human trials. Comprehensive long-term safety data for both peptides is still forthcoming.
Can MOTS‑c and SS‑31 be used together?
There is no official clinical evidence yet regarding combined use. However, since their mechanisms are complementary, MOTS‑c modulating systemic metabolism and SS‑31 reinforcing mitochondrial structure, there may be value in combined therapy under careful medical supervision. Always consult a medical professional.
Which peptide, MOTS‑c or SS‑31, is better for anti-aging?
Both show anti-aging promise through different avenues. MOTS‑c supports longevity pathways and physical endurance, while SS‑31 protects aging tissues by improving mitochondrial integrity. Use depends on whether systemic or targeted mitochondrial benefits are the focus.
What should I look for when purchasing MOTS‑c or SS‑31?
It is essential when sourcing these peptides, vendors must offer third-party purity testing, adhere to regulated manufacturing processes, and provide transparent documentation on dosage and handling especially for research use.
UAE Peptides meets all these criteria, offering high-quality peptides backed by transparency, compliance and efficient service
Are these peptides available to the public?
Yes, they are available to purchase from our partner website HERE and HERE
MOTS‑c and SS‑31 represent two distinct yet complementary approaches in mitochondrial medicine.
The right peptide for your needs depends on your specific health objectives, whether you’re looking to improve overall metabolic function or support mitochondrial integrity under stress. Consider factors such as safety, current evidence, and your practitioner’s guidance when making your decision.
Need help choosing the right peptide for your goals?
Book a consultation with one of our dedicated peptide research specialists to get personalised guidance and support.
Written by Elizabeth Sogeke, BSc Genetics, MPH
Elizabeth is a science and medical writer with a background in Genetics and Public Health. She holds a BSc in Genetics and a Master’s in Public Health (MPH), with a focus on mitochondrial science, metabolic health, and healthy aging. Over the past several years, she has worked with leading peptide research laboratories and functional medicine clinics, creating trusted, clinically-informed content that bridges the latest developments in peptide and longevity research with real-world applications.
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