Peptides

Longevity Essentials

On our journey to towards optimum wellness we observe our increasing dysfunctional symptoms: age spots on our skin, pinched nerves, headaches. An aging body becomes progressively worse at making proteins and better at breaking them down: we shift toward catabolism (we eat ourselves). This is why older adults lose muscle, bone density, and skin elasticity, and why maintaining adequate protein intake, resistance exercise, preserving growth hormone and supporting mitochondrial function are part of wellness.

Endogenous Peptides play a key role in our longevity. Exogenous Peptides are now options when our healing hits a wall.

Here’s an overview of what to know.

Peptides are Micro Proteins

Amino acids are the units, peptides are short chains of amino acids, and proteins are longer, more complex chains. Peptides and Proteins are assembled in every cell in this hierachie.

  1. Amino acids — individual molecules; the basic building blocks (20 standard types in proteins)

  2. Dipeptides — 2 amino acids linked together

  3. Oligopeptides — 3–20 amino acids (the prefix "oligo-" means "few")

  4. Peptides — short chains of fewer than 50 amino acids

  5. Polypeptides — chains of amino acids of any length (umbrella term)

  6. Proteins — typically ~50+ amino acids with a specific 3D structuresand biological functions

  7. Protein complexes — multiple proteins bound together (e.g., hemoglobin is made of 4 protein subunits)

  8. Multimeric assemblies — even larger structures where many proteins cluster together (e.g., ribosomes, which contain multiple proteins plus RNA)

Eating Essential Protein

Our 9 Essential Amino Acids – For a 154lb Adult

We have 20 amino acids of which these nine are genticaly encoded and used in translation.

  1. Histidine — immune function, neurotransmitter synthesis, anti-inflammatory roles

    • Daily requirement: ~700 mg (10 mg/kg)

  2. Isoleucine — muscle protein synthesis, branched-chain amino acid (BCAA)

    • Daily requirement: ~1,400 mg (20 mg/kg)

  3. Leucine — the primary trigger for mTOR signaling and muscle protein synthesis; most critical for anabolic response, especially with aging

    • Daily requirement: ~2,700–3,000 mg (39 mg/kg; higher ~43+ mg/kg for older adults doing resistance training)

  4. Lysine — collagen formation, bone health, immune function, calcium absorption

    • Daily requirement: ~2,100 mg (30 mg/kg)

  5. Methionine — methylation reactions, glutathione synthesis (master antioxidant), detoxification

    • Daily requirement: ~700–910 mg (10–13 mg/kg; can be partially spared by cysteine)

  6. Phenylalanine — precursor to tyrosine (dopamine, norepinephrine, thyroid hormones)

    • Daily requirement: ~1,750 mg (25 mg/kg; can be partially spared by tyrosine)

  7. Threonine — immune function, collagen and elastin synthesis

    • Daily requirement: ~1,050 mg (15 mg/kg)

  8. Tryptophan — precursor to serotonin and melatonin; mood, sleep regulation

    • Daily requirement: ~280 mg (4 mg/kg)

  9. Valine — muscle protein synthesis, BCAA, glucose metabolism

    • Daily requirement: ~1,820 mg (26 mg/kg)

There’s a reason farmers ate steak and eggs for breakfast to stay strong and live long.

  • 3 large eggs: ~18g protein, covers most EAAs well (especially leucine at ~1,260 mg)

  • 3.5 oz beef: ~26g protein, strong leucine (~1,400+ mg), excellent all-around

~44g protein, covers daily EAA needs

A Nutrients Module will sit before this Peptides Module. To include food combinations, plant & dairy, that yield the 9 EAAs. SHAKLEE has a Product > Cancer Immune Support

Wellness Data

What is Your Biological Age?

Amino Acid Dietary Adjustments ~ Age 50+

  • Leucine should trend higher: 43+ mg/kg to trigger mTOR more efficiently

  • Lysine emphasis: critical for collagen turnover (skin, joints, bone)

  • Methionine/cysteine balance: prioritize as methylation declines with age

  • Tryptophan: often deficient in older adults; impacts sleep quality and neurodegeneration

Iris reviews her Biological Age with Function Health Data

A story, a formula, a calculator, a widget links from here.

Our Organs Make Peptides

Peptides & Hormones by Organ & Tissue

These are our Endogenous Peptides. Specific anti-aging Peptides & Hormones are noted in green.

Adipose Tissue (Fat)

  • Leptin — appetite suppression, energy expenditure signaling

  • Adiponectin — insulin sensitivity, anti-inflammatory, metabolic health

    • Paradox: increases with weight loss, but lower in obesity (inverse relationship)

    • Protective against metabolic aging and neurodegeneration

    • Declines with visceral fat accumulation

Adrenal Gland

  • Cortisol — stress hormone, immune regulation, metabolism (produced in response to ACTH)

Brain & Central Nervous System (CNS)

  • Endorphins (β-endorphin, α-endorphin) — pain management, mood, pleasure, stress resilience

    • Source: Anterior pituitary + hypothalamus + brain neurons

    • Decline with age; linked to depression, chronic pain, reduced stress buffering

  • Enkephalins (met-enkephalin, leu-enkephalin) — pain modulation, reward signaling

    • Source: Neurons throughout CNS (spinal cord, brainstem, limbic system)

    • Dysregulation in chronic pain states and aging

  • Neuropeptide Y — appetite, anxiety, circadian regulation

  • Substance P — pain and emotion processing

  • Neurotensin — pain regulation, neuromodulation

  • Kisspeptin — reproductive hormone signaling

  • TRH (thyrotropin-releasing hormone) — stimulates thyroid and prolactin

  • GnRH (gonadotropin-releasing hormone) — reproductive hormone cascade

  • CRH (corticotropin-releasing hormone) — stress response (stimulates ACTH)

Heart

  • ANP (atrial natriuretic peptide) — sodium/fluid excretion, blood pressure lowering

  • BNP (B-type natriuretic peptide) — heart failure signaling

Kidneys

  • Renin — initiates blood pressure regulation cascade

  • Erythropoietin (EPO) — red blood cell production, mitochondrial oxygenation, neuroprotection

    • Produced by renal interstitial fibroblasts

    • Declines with age and kidney dysfunction

    • Critical for oxygen delivery (brain, muscle, mitochondria)

    • Emerging evidence for direct neuroprotective signaling

Liver

  • IGF-1 (insulin-like growth factor-1) — muscle/bone anabolism, longevity signaling

    • Produced in response to growth hormone signaling

    • Peaks in youth; declines ~14–20% per decade

    • Anabolic but requires careful balance (excessive IGF-1 has longevity trade-offs)

  • Angiotensinogen — precursor for renin-angiotensin system (blood pressure)

Pancreas

  • Insulin — glucose regulation, anabolic signaling (beta cells)

  • Glucagon — raises blood glucose, mobilizes energy (alpha cells)

  • Growth hormone (GH/somatotropin) — anabolic driver, lipolysis, longevity central

    • Source: Anterior pituitary (somatotroph cells)

    • Declines sharply (~14%/decade after age 30)

  • Somatostatin — inhibits insulin & glucagon secretion (delta cells)

  • Pancreatic polypeptide (PP) — regulates digestive secretions (PP cells)

Parathyroid Glands

  • PTH (parathyroid hormone) — raises blood calcium, regulates phosphate and vitamin D, bone resorption, calcium mobilization

    • Source: Parathyroid glands

    • Critical as estrogen/testosterone decline (menopause/andropause accelerates bone loss)

    • Dysregulation contributes to osteoporosis

  • Calcitonin — bone resorption inhibition, calcium/phosphate regulation

    • Source: Thyroid gland (parafollicular C-cells)

    • Declines sharply in postmenopausal women (less inhibition of bone loss)

Pituitary Gland

  • Growth hormone (GH/somatotropin) — muscle/bone synthesis, lipolysis, longevity

  • Prolactin — lactation, reproductive function

  • ACTH (adrenocorticotropic hormone) — stimulates cortisol from adrenal gland

  • TSH (thyroid-stimulating hormone) — thyroid function

  • FSH/LH (follicle-stimulating/luteinizing hormone) — reproductive hormones

  • Oxytocin — bonding, uterine contraction, social behavior

  • Vasopressin (ADH) — water reabsorption, blood pressure regulation

Reproductive Organs (Ovaries/Testes)

  • Inhibin — FSH suppression

  • Activin — FSH stimulation

  • Various peptide regulators of reproductive cascade

Small Intestine (Enteroendocrine Cells)

  • GLP-1 (glucagon-like peptide-1) — glucose regulation, appetite suppression, neuroprotection

    • Declines with age; now major target of longevity research (semaglutide, tirzepatide)

  • GIP (glucose-dependent insulinotropic polypeptide) — insulin secretion, satiety

  • Peptide YY (PYY) — appetite suppression, gut motility

  • CCK (cholecystokinin) — gallbladder contraction, digestive enzyme release, satiety

  • Secretin — pancreatic bicarbonate secretion, pH regulation

  • Motilin — gastric motility

  • Substance P — pain signaling, immune function

  • VIP (vasoactive intestinal peptide) — smooth muscle relaxation, secretions

Thymus Gland

  • Thymosin (thymosin α1, thymosin β4) — T-cell development, immune function

    • Source: Thymic epithelial cells

    • Dramatic shrinkage starts in childhood, accelerating after age 40

    • Declines ~3% per year; by age 60–70, thymus is largely fat

    • Central to immunosenescence (aging immune system, reduced vaccine response, infection vulnerability)

  • Thymopoietin — T-cell maturation

Thyroid Gland

  • Calcitonin — calcium/phosphate regulation, bone resorption inhibition

Work With Your Health Practitioner

Taking care of the organs in your body that make your peptides is guided by diagnostic measuring as well as your Functional Genomics.

Testing Lists

Peptide Discovery Timeline

Key Developments & Decisions

1882–1954 First peptide synthesis; discovery of secretin, insulin, oxytocin

1963–1980s SPPS invention; recombinant technology; USA FDA approves 80+ peptide drugs

1990s–2022 Peptides widely used in compounding pharmacies; no major USA FDA restrictions

Sept 2023 USA FDA moves 19 peptides to Category 2 (restricted)

Feb 27, 2026 14 peptides move back to Category 1

April 23, 2026 19 peptides officially removed from Category 2

July 23–24, 2026 PCAC meets to formally evaluate peptides for Category 1 status

February 2027 Second PCAC meeting

Healing Injuries

Renner's memoir details his near-fatal 2023 snowplow accident, his intensive recovery protocol, and his reflections on endurance and family.

Jeremy Renner’s aggressive recovery protocol

His 38 broken bones relied heavily on advanced regenerative medicine and cellular therapies. While he hasn't released a strict medical schedule, his regimen combines specific peptides for tissue healing and hormone optimization with holistic therapies. His recovery was heavily driven by a strict daily physical therapy schedule and a positive mindset.

Key Components of Renner's Protocol:

  • Tissue-Repair Peptides: Renner has explicitly mentioned using peptides like BPC-157 and Mots-c, which are highly touted in regenerative medicine for accelerating soft tissue repair, reducing inflammation, and promoting angiogenesis (new blood vessel development).

  • Hormone Optimization: His functional medicine approach included testing and optimizing hormones, specifically focusing on Testosterone and Growth Hormone, which are vital for rebuilding muscle mass and bone density.

  • Cellular Energy: He incorporates NAD+ (nicotinamide adenine dinucleotide) via subcutaneous and intramuscular injections to boost cellular health and speed up recovery.

  • Physical & Regenerative Modalities: The peptide stack was paired with Hyperbaric Oxygen Therapy (HBOT) at 2.0 atmospheres, red light/infrared therapy, cryotherapy (cold chambers), and intravenous drips.

Featured Interviews & Podcasts

  • The Joe Rogan Experience: A deep-dive, long-form conversation exploring his survival mindset, the mechanics of his physical trauma, and the extensive medical and holistic modalities he utilized during his intense recovery.

  • SmartLess Podcast: An in-depth conversation covering his recovery mindset, career trajectory, and life adjustments following his accident.

  • Let's Talk Off Camera with Kelly Ripa: An episode where he opens up about his road to recovery, the support of his Marvel co-stars, and how previous life experiences unexpectedly prepared him for survival.

  • Armchair Expert with Dax Shepard: A wide-ranging retrospective interview discussing his early career as a makeup artist, his initial real estate investments, filming The Hurt Locker, and his connection to the Marvel community.

Reclassification of Synthetic Peptides

Exogenous Peptides

Synthetic Exogenous Peptides that are not naturally produced by a mammalian body in large amounts. We can imagine them as different concentrated syrups.

This list of peptides may once again be federally legal to compound at pharmacies. To be approved for research and off-label use with a valid physician prescription pending the downgrade to Category 1 – Meeting July 23-24, 2026 by USA FDA.

  • AOD-9604

  • BPC-157 (Body Protection Compound-157) is a 15 amino acid peptide derived from a protective protein found in gastric juice.

    • Gut barrier repair (tight junction integrity)

    • Angiogenesis (blood vessel formation)

    • Neuroplasticity, nerve regeneration

    • Anti-inflammatory, reduces nitric oxide dysfunction

    • GI healing, IBS/ulcer relief

  • Evidence status:

    • Animal studies: promising for gut healing, neuroprotection, tendon repair

    • Human studies: very limited; mostly anecdotal or small case reports

  • Longevity angle: Gut barrier integrity is linked to aging, inflammation, and cognitive decline. If evidence accumulates, BPC-157 could be relevant for aging-related permeability.

  • CJC-1295 (GHRH Analog) + Ipamorelin (GHRP Analog) is a synthetic analog of growth hormone-releasing hormone (GHRH)

    • Ipamorelin: Synthetic selective ghrelin receptor agonist (GHRP mimic)

    • Often stacked together to synergize GH release

  • Claimed mechanisms:

    • Growth hormone secretion — both stimulate GH release from anterior pituitary

    • Synergistic effect — CJC-1295 (GHRH pathway) + Ipamorelin (ghrelin pathway) = greater GH pulse than either alone

    • Muscle anabolism — via elevated GH → IGF-1

    • Fat loss — GH-mediated lipolysis

    • Recovery & sleep — GH is secreted during deep sleep

    • Bone density — GH-IGF-1 axis supports bone remodeling

  • Evidence status:

    • Animal & limited human studies: both stimulate GH as claimed

    • Human efficacy data: CJC-1295 has more research; Ipamorelin emerging

    • Safety profile: short-term tolerability appears reasonable; long-term human data lacking

  • Comparison to natural GH stimulation:

    • Exercise, sleep, fasting, and time-restricted eating also boost GH naturally

  • DSIP

  • Epitalon

  • GHK-Cu (Copper Tripeptide / Ghk-Copper) is a naturally occurring tripeptide (glycine-histidine-lysine) + copper in a 3:1 ratio

    Collagen synthesis — stimulates types I, III, IV collagen production

    • Wound healing — angiogenesis, fibroblast proliferation

    • Anti-inflammatory — reduces TNF-α, IL-6

    • Skin aging — firmness, elasticity, wrinkles (marketed heavily in cosmetics)

    • Hair growth — some claims for hair density (topical application)

    • Antimicrobial — copper's inherent properties

    • Tissue remodeling — matrix metalloproteinase regulation

In vitro & animal studies: solid for collagen upregulation

  • Human studies: limited; mostly small studies or manufacturer-sponsored

  • Bioavailability: Topical GHK-Cu (skin serums) has questionable penetration; oral/injectable forms are still rare

  • Ipamorelin

  • Kisspeptin-10

  • KPV

  • MOTS-C

  • Selank

  • Semax

  • TB-500 (Thymosin Beta-4) is a naturally occurring peptide (44 amino acids) found in blood and tissues

    • Highest concentrations in platelets, bone marrow, thymus

    • Declines with age

  • Claimed mechanisms:

    • Tissue repair & regeneration — angiogenesis, fibroblast migration, myogenic differentiation

    • Anti-inflammatory — reduces TNF-α, IL-6, NF-κB pathway

    • Wound healing — faster epithelialization

    • Muscle recovery — some claims for exercise recovery (anecdotal)

    • Hair growth — topical + systemic claims (limited evidence)

    • Joint health — cartilage repair, tendon healing

  • Evidence status:

    • In vitro & animal studies: solid for tissue repair and inflammation

    • Human studies: very limited; mostly small, non-randomized

  • Thymosin Alpha-1

Peptide Experts

Subject Investigators

Attia Skeptical longevity expert. Critical frameworks, hype evaluation

Dawson. Academic chemist. Understanding peptide synthesis & development

Gillett Education-focused. Hormone optimization, peptide combinations

Huberman Evidence-based, cautious. Mechanism, safety, realistic expectations

Koniver Pragmatic clinician. Practical protocols, sourcing, physician models

Dr. Peter Attia (Longevity Medicine)

Phil Dawson, PhD (Scripps Research - Academic Peptide Chemistry)

  • Institution: Department of Chemistry, Scripps Research

  • Award: 2024 Cathay Award from Chinese Peptide Society (highest honor)

  • Focus: Chemical synthesis, chemoselective approaches to peptide drug discovery

  • Relevance: Leading academic voice on peptide chemistry and peptide materials science

  • Research direction: Advanced manufacturing and synthetic peptide development

Dr. Kyle Gillett (Hormone Optimization & Obesity Medicine)

  • Board-certified: Family medicine + obesity medicine

  • Primary education platform: Free social media (zero-cost-to-consumer)

    • Instagram: @kylegillettmd

      • Website: https://kylegillettmd.com

      • Platform: gilletthealth.com

      • Podcast: The Gillett Health Podcast

      • Social handles: @gilletthealth (X, LinkedIn, TikTok, Facebook, YouTube)

    • Huberman Lab appearances: Multiple (hormone optimization, peptides, male & female health)

    • Key focus: Peptide dosing, GHRP protocols, BPC-157 for tissue healing, testosterone optimization

    • Recent (2026): Peptide MASTERCLASS episode on The Neuro Experience

Andrew Huberman (Stanford Neuroscientist)

Primary platform: Huberman Lab Podcast

  • Website: https://www.hubermanlab.com

  • Peptide-focused episode (2024): "Benefits & Risks of Peptide Therapeutics for Physical & Mental Health"

  • Latest (March 2026): Goop interview on peptide stacking and GLP-1s

  • Social: @hubermanlab (Instagram, X)

  • Key focus: Mechanism, safety, and evidence-based peptide use; NOT promotional

Dr. Craig Koniver (Performance Medicine)

  • Board-certified physician (family medicine, trained at Brown & Thomas Jefferson)

  • Huberman Lab episode: "Peptide & Hormone Therapies for Health, Performance & Longevity" (Oct 2024)

  • Practice focus: 15+ years peptide prescribing experience; concierge medicine (Charleston, SC)

  • Podcast appearances: Vibrant Wellness Podcast (Oct 2025), multiple longevity-focused platforms

  • Specializations: BPC-157, GLP-1s, growth hormone secretagogues, NAD therapy

  • Key message: Sourcing quality, physician oversight, distinction between research vs. clinical use

Work With Your Health Practitioner

Taking care of the organs in your body that make your peptides is guided by diagnostic measuring as well as your Functional Genomics.

Testing Lists

Know Your Genomic Peptide Dimmer SNPs

Specific aging ones related are noted in green.

Adipose Tissue – Adiponectin

ADIPOQ Gene:

  • rs2241766 (+45T/G, exon 2) — G allele associated with lower adiponectin levels

    • GG genotype: 2.53× higher metabolic syndrome risk

    • Affects mRNA stability/splicing

  • rs1501299 (+276G/T, intron 2) — T allele associated with reduced adiponectin

    • Associated with hyperglycemia, metabolic syndrome

    • GG+TG: 1.42× metabolic syndrome risk

  • rs266729 (−11377C/G, promoter) — reduces ADIPOQ transcription

  • rs17366743, rs10937273, rs17300539, rs182052 — all associated with reduced adiponectin production in T2D

  • rs822396, rs17846866, rs3774261, rs822393 — multiple SNPs linked to adiponectin deficiency across diabetes types

Anterior Pituitary

GH1 (Growth Hormone Gene):

  • rs7208736 — minor allele associated with lower fasting GH (p = 5.15×10⁻⁶)

    • Associated with lower BMI and waist circumference in males

GHR (Growth Hormone Receptor Gene):

  • rs13153388 — elevated GH levels but reduced height (suggests GHR insensitivity; compensatory GH elevation)

  • rs17574650 (intron 1) — rare variant (MAF <3%)

  • rs6180 (exon 10) — associated with idiopathic short stature

  • GT-repeat microsatellite in 5′UTR — L/S genotype 3.3× higher risk of short stature in children

  • M/S genotype — 1.9× more frequent in male short stature

Brain/Central Nervous System – Endorphins & Enkephalins

PENK (Proenkephalin), POMC (Pro-opiomelanocortin) genes:

  • OPRM1 (Opioid Receptor Mu-1) SNPs affect receptor sensitivity, indirectly affecting endorphin feedback loops

  • rs1799971 (OPRM1 A118G) — affects opioid signaling & pain perception (not direct production, but functional impact)

Kidneys – Erythropoietin

EPOR (EPO Receptor) variants:

  • Direct EPO production SNPs are rare in the literature

  • Kidney function decline → reduced EPO production (age/disease-related, not genetic SNPs primarily)

Liver

IGF1 Gene SNPs (Promoter & Coding):

  • rs35767 — TT & CT+TT genotypes correlated with elevated osteoporosis risk (OR 1.90 & 1.35)

    • Indicates reduced IGF-1 function/production

    • 2.11× increased risk in smokers/drinkers

  • rs2288377 — associated with lower IGF-1 levels in bone mineral density studies

  • rs5742612 — contributes to reduced bone formation phenotype

  • rs2162679 (IGF1) — AA genotype 2.2× higher myopia risk, suggesting altered growth signaling

  • rs1019731, rs12821878 — associated with breast cancer (IGF-1 pathway dysregulation)

Rare variants identified in centenarians:

  • A118T variant — located at E-peptide cleavage site; affects mature IGF-1 release

Pancreatic Beta Cells

INS Gene:

  • rs689 (−23/Hph1 A>T) — strongest non-HLA association with Type 1 Diabetes

    • Associated with short class I VNTR alleles

    • Reduced insulin production (autoimmune destruction)

    • OR = 1.81, p = 2.34×10⁻⁴⁵ in multi-ancestry GWAS

    • An allele associated with reduced INS gene expression in pancreas

  • VNTR class I alleles (rs689-tagged) — decreased INS expression relative to class III

Small Intestine – Enteroendocrine L-cells

GLP1R (GLP-1 Receptor — affects endogenous GLP-1 axis feedback):

  • rs6923761 (Gly168Ser, G>A) — minor A allele frequency 29% in Europeans

    • Alters GLP-1R function; affects glucose-dependent insulin secretion

    • Associated with delayed gastric emptying response to GLP-1 agonists

  • rs761387 — modifies oral semaglutide response

  • rs2268640 — suggestive genome-wide significance for GLP-1 response

  • rs10305420 (Pro7Leu C>T) — potentially alters GLP-1R response

  • rs10305510 (R421P)

  • rs140642887 (A239T)

  • rs149578908 (R310Q)

  • rs182447758 (R227H)

  • rs202171972 (D344E)

  • rs2235868 (R176G)

Parathyroid & Thyroid – PTH & Calcitonin

Limited SNP data, but relevant variants:

  • CASR (Calcium-Sensing Receptor) variants — affect PTH secretion sensitivity

  • VDR (Vitamin D Receptor) SNPs — regulate PTH/calcium axis indirectly

Thymus Gland – Thymosin

Limited direct genetic studies; immunosenescence-related:

  • Thymus involution is age-dependent, not SNP-driven primarily

  • However, IL-7 receptor SNPs and T-cell development genes (IKZF1, GATA3) may indirectly affect thymosin-mediated T-cell maturation

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