Introduction to Peptidology: A Comprehensive Guide

In this guide, we delve into the emerging field of clinical peptidology, which explores peptides from various perspectives including their presence in the environment, methods of extraction or chemical synthesis, their role as regulators within the body’s internal environment, their involvement in disease pathogenesis and functional disorders, and the diverse applications of peptides in pharmaceuticals, nutraceuticals, functional foods, and dietary components. This contemporary view on clinical peptidology is presented through the lens of healthy aging and functional capacity, individual vitality, its domains, and the risk factors for their impairment. The guide is designed for a broad audience interested in peptides and health, providing insights into the principles of modern clinical peptidology.

Peptidology Explained

Modern medicine is rapidly advancing, integrating new diagnostic, therapeutic, and rehabilitation technologies. A crucial aspect of this progress is the application of contemporary scientific knowledge, which enables the introduction of modern medications into clinical practice, achieving significant clinical outcomes. Peptides, in particular, represent a new generation of therapeutics with diverse applications not only as drugs, vaccines, and nutraceuticals but also as essential components of the body’s internal environment, used in disease diagnostics and therapy effectiveness assessments. Peptides are also studied as signaling agents that regulate vital biological processes.

Clinical peptidology stands at the crossroads of fundamental science, clinical medicine, environmental science, and industrial production, focusing on peptides in human internal environment regulation, environmental peptide sources and extraction methods, quantitative peptide measurement in homeostasis regulation and therapeutic efficacy assessment, and their use in prevention, treatment, and rehabilitation.

Peptides in the Environment

The environment plays a crucial role in human health as a source of nutrients essential for life. The Mediterranean diet, recognized for its health benefits in preventing cardiovascular diseases, dementia, and cancer, includes plant and animal peptides that prevent primary sarcopenia, characterized by reduced muscle strength and mass. This guide emphasizes the importance of dietary peptides and essential amino acids in food to stimulate postprandial muscle protein levels. It also highlights the significance of exercise variety and quality as part of a healthy lifestyle focused on muscle health throughout the human lifecycle.

Resilience Diet for Optimal Peptide Intake

We introduce the concept of a resilience diet designed to enhance human vitality, advocating for moderate but sufficient caloric intake, a diet rich in plant-based peptides and fibers, and limited consumption of easily digestible carbohydrates like potatoes to avoid obesity and diabetes. The diet emphasizes the importance of diverse protein sources, including poultry, fish, legumes, and nuts, to meet the increased protein and peptide needs of aging individuals. It also suggests minimizing sugar intake to maintain brain function while avoiding excessive sugar consumption.

This comprehensive guide to peptidology not only covers the scientific and clinical aspects of peptides but also provides practical advice on leveraging dietary peptides for health and wellness, reflecting the modern trend of utilizing natural peptides in healthy lifestyle practices.

Peptides and the Body’s Internal Environment: The Path to Healthy Aging

Research in gerontology, since its inception, has been focused on identifying processes specific to aging. With over 200 theories attempting to explain the multifaceted changes at various levels—from the organism as a whole, its systems and organs, down to the cellular and molecular levels—our understanding of aging continues to evolve.

In the realm of geriatrics, aging is classified into three types: natural (physiological) aging, characterized by a specific pace and sequence of age-related changes aligned with the biological and adaptive-regulatory capacities of the human population; slowed (retarded) aging, marked by a slower pace of age-related changes, with longevity as its extreme manifestation; and premature (pathological, accelerated) aging, noted for the early onset or pronounced manifestation of age-related changes during certain life stages.

Even normal aging is associated with a decreased ability to adapt to environmental changes, making the body more susceptible to diseases and injuries. As aging progresses, all organs and systems undergo significant transformations, affecting body size, shape, composition, facial features, and skin, which become focal points in aesthetic medicine.

Height reduction in aging is primarily due to the flattening of intervertebral discs and the development of senile kyphosis. Body mass notably decreases in old age, especially among the long-lived, with muscle mass peaking between 20–30 years and gradually declining thereafter, particularly after 50. This decline in muscle mass and strength is a clear sign of aging.

The distribution of subcutaneous fat changes with age, moving from the cheeks to the lower face, accentuating the cheekbones, and accumulating under the chin, chest, and abdomen. It is generally believed that the peak of physical condition occurs around 25 years, with signs necessitating aesthetic medical intervention starting after 40 years. Thus, the optimal age for starting peptide use is generally 40 years, although indications can arise as early as 18, without age limitations thereafter.

The modern doctrine of healthy aging emphasizes three key principles for preventive programs: healthy aging doesn’t imply disease absence but rather good functional ability enabling an active social life; it’s shaped throughout a person’s life cycle, starting from infancy, aiming to delay age-related diseases and reduce the burden of late-life illnesses, thus shortening and alleviating the “red” period of life; and it’s currently gauged based on an individual’s vitality, i.e., health characteristics in terms of various functional domains.

Healthy Aging Across the Human Life Cycle

After 60, the average number of chronic conditions varies between 4 to 7, and the focus shifts from disease prevention to mitigating their progression and maintaining good functional ability, which allows an individual to live according to their social needs and preferences.

Contemporary preventive anti-aging medicine starts from infancy. For example, breastfeeding is known to reduce morbidity in later life stages, as substituting breast milk with commercial formulas high in unbalanced nutrients and calories leads to obesity, which in turn is linked to various chronic non-communicable diseases. Conversely, malnutrition in infancy can lead to growth and developmental delays, weakening immune competence and cognitive, behavioral, and motor abilities, laying a foundation for decreased functionality in older age.

Healthy Aging and Individual Vitality

Individual vitality, a core concept in gerontology and geriatrics, is integral to understanding and fostering healthy aging. This includes managing syndromes like frailty, which results from diminished physiological reserves and increased vulnerability to adverse health outcomes. Gerontology, geriatrics, and anti-aging medicine don’t just focus on the latter half of life but extend preventive measures across all age groups.

In conclusion, peptides play a pivotal role in this modern approach to aging, offering therapeutic, preventive, and rehabilitative benefits as part of comprehensive health and longevity strategies. Through understanding and addressing the factors affecting individual vitality throughout life, we can better formulate preventive programs that incorporate peptides, nutrition, and lifestyle adjustments to support healthy aging.

Risk Factor Tree Analysis for Individual Vitality Domains

Cognitive Domain

• Repeated traumatic brain injuries
• Sleep disturbances
• Smoking
• Excessive alcohol consumption
• Benign age-related forgetfulness

Somatic Domain

• Inflammation
• Age-related immune dysfunction
• Non-alcoholic fatty liver disease
• Hypothyroidism, including subclinical
• Cholesterol metabolism disorders
• Borderline hypertension
• Excessive body weight and metabolically healthy obesity
• Exposure to fine particulate matter from hydrocarbon combustion
• Adherence to a Western diet
• Orthostatic hypotension

Psychological Domain

• Social constructs and their health impact – “normalization of menopause,” “normalization of andropause”
• Anxiety and depression

Sensory Domain

• Hearing loss
• Vision impairment
• Diminished sense of smell

Locomotor Domain

• Reduced muscle strength
• Sedentary lifestyle
• Arthritis of various locations

Peptides and the Key Domains of Individual Vitality

Locomotor Domain Modern views consider bones and muscles as a unified system regulated by peptide substances, including myokines produced by muscles and osteokines produced by bones. Recently, special attention has been given to peptides produced by white adipose tissue, known as adipokines. Research has shown that regulatory peptides, especially those released by white adipose tissue located between muscle fibers, contribute to the development of osteopenia, dynapenia, and, overall, sarcopenic obesity with significant metabolic consequences. It’s important to note that not only abdominal obesity but also intramuscular fat deposition matters.

Key myokines include interleukins such as IL-6, which has anti-inflammatory effects when produced by muscles and increases glucose consumption by muscle tissue and induces osteoclast activity; IL-7 and IL-15, which are pro-inflammatory and increase osteoclast activity leading to bone resorption. Myostatin, activated by insufficient muscle activity or muscle injury, is a crucial myokine in sarcopenia development, enhancing osteoclast activity and bone tissue resorption. Growth factors like IGF-1, activated by physical activity, promote osteoblast activation and bone tissue recovery; IGF-2, expressed in response to membrane damage, activates osteoblasts; and FGF-21, expressed in muscles in response to insulin, contributes to bone tissue resorption. Irisin, produced by muscle and fat tissue, increases glucose consumption in muscles and activates fibroblasts in bones.

Key osteokines include uncarboxylated osteocalcin, secreted by osteoblasts, which enhances insulin sensitivity, increases glucose consumption by muscles, and improves muscle strength (proven in animal studies); and signaling molecules from osteocytes that inhibit muscle cell differentiation and reduce muscle tissue formation activity; SOST molecule, produced by osteocytes, inhibits osteoblast formation and slows down bone tissue formation rate.

Adipokines, peptide-based signaling molecules, include adiponectin, which increases with a reduction in fat tissue volume, has an anti-inflammatory effect, and enhances glucose consumption and fatty acid degradation in the bone-muscle system. Leptin, associated with obesity, intensifies inflammation, reduces bone mineral density, inhibits free fatty acid degradation, and in fat tissue, hampers fatty acid degradation.

Understanding the biochemical interactions between muscle, bone, and fat tissues, which are largely peptide-based, is crucial for addressing risk factors in the locomotor domain of individual vitality. Proper nutrition and physical activity, known to activate the production of endogenous peptides like FGF23, BMP7, and LCN2, play a significant role in this context.

Somatic Domain Increasing physical activity levels, in line with current WHO recommendations, is a well-established and justified approach for managing risk factors for many somatic diseases. It’s advised to engage in moderate-intensity aerobic physical activity for at least 150-300 minutes per week, or vigorous-intensity aerobic physical activity for 75-150 minutes per week, or an equivalent combination of moderate- and vigorous-intensity activity throughout the week. Muscle-strengthening activities for all major muscle groups should be done at least twice a week for additional health benefits. Time spent sitting or lying down should be limited, and sedentary time should be replaced with physical activity of any intensity for health benefits.

Starting with anaerobic loads, such as resistance exercises, and then incorporating aerobic exercises, followed by stretching and balance exercises (e.g., Tai Chi for older adults), can help make physical activity a routine for better health. The modern principle of healthy behavior suggests filling even the smallest breaks with physical activity (“no rest”).

Regular physical activity positively impacts the somatic domain and other individual vitality domains, reducing mortality, cardiovascular diseases, hypertension, certain cancers, and preventing falls and frailty in older age groups, as well as obesity.

Cognitive Domain The world of peptides is multifaceted, and in the context of the cognitive domain, it’s important to note that peptides can play both negative and positive roles. For example, peptides are involved in the development of Alzheimer’s disease, but this knowledge is being used to create new drugs that could potentially treat neurodegenerative dementias. Various peptides and proteins, including amyloidogenic ones like beta-amyloid peptide (Aβ), Tau protein, and prion protein PrP, are implicated in Alzheimer’s disease pathogenesis. Aβ peptide accumulation outside neurons forms fibrils and amyloid plaques. Current treatment strategies focus on disrupting extracellular Aβ deposits, which could lead to the formation of small aggregated Aβ molecules (oligomers) with toxic effects on neuron function and cell survival. The biological role of Aβ peptide in normal conditions remains largely unknown, though its isoforms of varying lengths are found in people of all ages, regardless of disease symptoms. Aβ peptides might play a role in brain signaling pathways and have neuroprotective properties at low concentrations. Aβ oligomers are crucial in Alzheimer’s disease pathogenesis, exerting toxic effects on neurons. Professor Dieter Willbold developed a D-enantiomeric peptide, D3, and its derivatives to dismantle and destroy cytotoxic small oligomers, with one such compound currently in phase II clinical trials. This example illustrates how clinical peptidology’s focus on peptide involvement in disease pathogenesis expands the horizons for scientific development and clinical testing of new pharmaceuticals.

Psychological Domain and Peptide Therapy

The psychological state and mood are significantly influenced by polypeptide molecules known as endorphins, which are chemically similar to opiates and produced by brain neurons. Endorphins are well-known for their analgesic properties, and their production increases in response to stress, modulating the activity of organs and systems to form adaptive reactions and counteract the development of post-stress disorders. In many pathological conditions, especially those with significant pain syndromes, depression, or psychological disorders, patients exhibit depletion of the endorphinergic system and reduced baseline endorphin levels (endorphin deficiency).

To enhance endorphin levels and correct the psychological domain of individual vitality, both natural and artificial methods are employed. Activities such as listening to favored music (music therapy), engaging in sports, experiencing new positive impressions, dietary indulgences, and other enjoyable actions naturally increase blood endorphin levels, improving mood, well-being, and psychological status. However, this occurs only when the endorphinergic structures function normally. For correcting disorders and aiding in diseases, this is insufficient. The introduction of endorphins and their synthetic analogs, including peptide therapy, is necessary.

Peptide Therapy and Action Mechanism

Peptides can fundamentally be classified based on their origin into natural (animal, plant, marine) and synthetic; by application method into oral and injectable (intradermal); and by registration nature as pharmaceutical drugs, dietary supplements, or components of diet, sports, and functional nutrition.

Experimentally, it has been established that short peptides regulate gene activity through complementary binding to specific DNA segments, demonstrating genospecific tropism and direct involvement in epigenomic regulatory mechanisms. Embedded peptides transmit information to specific cell types for tissue-specific protein synthesis. This means that a particular peptide with a specific amino acid sequence targets strictly defined biological processes within the cell.

The pathogenetic mechanism of peptide regulation can be summarized as follows: complementary interaction of short peptides with DNA; alteration in gene expression (activity) and activation of specific protein production; regulation of biochemical and physiological processes (anti-aging effect). Short peptides do not function on a “substitution” therapy principle but modulate the genetic apparatus of the cell and regulatory processes, leading to the most rational cell functioning mode.

From a contemporary perspective, the protective effects of bioregulatory peptides are considered within the interdisciplinary field of general pathology – neuroimmunoendocrinology. Recent decades have seen significant shifts in traditional homeostasis regulation concepts. Numerous studies have revealed that various cells from the nervous, immune, and endocrine systems produce identical signaling molecules – peptide hormones, biogenic amines, and polyunsaturated fatty acid derivatives.

This characteristic applies to all human body organs and systems. Here, we’ll explore the protective effects of bioregulatory peptides using skin as an example. Nerve cell endings, Merkel cells, endotheliocytes of skin vessels, immunocompetent cells (Langerhans cells, epidermal T-lymphocytes, monocytes/macrophages, mast cells), keratinocytes, and melanocytes can, under certain conditions, activate the production of signaling molecules identical to those produced by the central nervous, endocrine, and immune systems. Skin homeostasis adheres to universal intercellular interaction laws, and modern aesthetic medicine seeks the most effective agents to modulate this interaction in the most physiological ways.

Bioregulatory peptides influence two “targets” – the neuroimmunoendocrine unit of the epidermis and the neuroimmunoendocrine unit of the dermis, enhancing their activity in a way that gene expression leads to increased production of beneficial anti-aging signaling molecules and inhibits the production of pro-aging molecules.

The use of bioregulatory peptides can thus be viewed as “targeted” anti-aging therapy, restoring the neuroimmunoendocrine regulatory scheme of the skin characteristic of a younger age. Topically applied biomimetic peptides exert multiple effects through signaling molecules. To discuss these, it’s necessary to clarify the concepts of the neuroimmunoendocrine units of the epidermis and dermis.

The neuroimmunoendocrine unit of the epidermis encompasses signaling molecules that ensure functions such as physical barrier maintenance, pigmentation, immune activity, sensitive reception, metabolic transformations, and vitamin D production. The neuroimmunoendocrine unit of the dermis comprises signaling molecules that support structural integrity, thermoregulation, sensitive reception, vascular activity regulation, immune activity, exocrine secretion, and metabolic reactions.

On a molecular level, “targeted” effects of bioregulatory peptides involve enhancing the expression of genes responsible for producing key signaling molecules: anti-inflammatory interleukins, epidermal growth factor, fibroblast growth factor, insulin-like growth factor, intercellular adhesion molecules, and anti-apoptotic factors, whose production by neuroimmunoendocrine cells decreases with age, leading to skin aging manifestations such as structural changes, sensitivity reduction, vascularization decrease, immune activity decline, pigmentation increase, and reduced growth activity of skin appendages, including hair. Peptides shift the balance of anti-aging/pro-aging factors towards anti-aging factors, reducing the relative content of neuroimmunoendocrine “aging” molecules. These primary molecules include pro-inflammatory interleukins, tumor necrosis factor-alpha, monocyte chemoattractant protein, and colony-stimulating factors – granulocyte-macrophage, granulocyte, and monocyte-macrophage. These signaling molecules, by affecting skin immunocytes and endothelial cells, contribute to the intensification of chronic immune inflammation, which becomes constant and pronounced with age.

Shifting the balance towards anti-aging factors positively impacts pathological processes like apoptosis, proliferation, and chronic immune inflammation, yielding significant local clinical effects.

Peptide use represents a fundamentally new approach in treatment and prevention. Their uniqueness lies in the drug’s ability to influence the cell genome, promoting gene expression and enhancing the production of specific proteins with beneficial sanogenic or therapeutic effects. The amount and degree of synthesized protein are determined by the cell’s potential and regulated by intricate intracellular mechanisms, ensuring the physiological impact of short peptides, crucial in practices like aesthetic medicine.

In some cases, replacement therapy is the method of choice, such as in bilateral oophorectomy at a young age, among others. However, replacement therapy’s drawback is the inability to precisely determine the amount of agent administered, which can adversely affect cells and tissues in some instances. Growth factor replacement therapy, widely used in aesthetic medicine, undoubtedly has advantages. Yet, determining the exact concentration and volume of the administered drug required in a particular case is challenging, leading to side effects like enhanced immune inflammation, hypervascularization, etc. Therefore, the use of short peptides in clinical medicine is a physiological, sparing method that allows for another approach adopted in modern clinical practice, namely, the “individualized” impact.

Peptide Side Effects

Peptide side effects include allergic reactions and individual intolerance. In high doses, oral peptide drugs have been associated with irritable bowel syndrome. Nonspecific side effects of topical use in dermatocosmetology include iatrogenic errors during intradermal administration, leading to infection and neuritis.

Overall, peptide drugs are well-tolerated, but allergy history should be clarified before their use. In case of past allergic reactions, caution is advised, including allergy testing and subsequent dynamic monitoring.

Conclusion

Peptides are a group of drugs used in medicine and healthcare, based on a short sequence of amino acids that influence the activation of endogenous anti-aging signaling molecule production while reducing the relative concentration of pro-aging molecules. Thus, these drugs are “targeted” in their action. The contemporary use of short peptides is based on the principles of individuality, aging rates, and is aimed at supporting health and functionality across the domains of individual vitality. Short peptides have some side effects, including individual intolerance and allergic reactions, but are generally well-tolerated and can be recommended to a wide audience.