Epithalon

1. Studied for

   Telomerase activity and telomere length in human cell lines

   In telomerase-negative human fetal fibroblasts grown in culture, adding Epithalon was reported to induce expression of the telomerase catalytic subunit, measurable telomerase enzymatic activity, and telomere elongation; the authors read that as reactivation of the telomerase gene and proposed it could extend the lifespan of a cell population, a step beyond what the experiment itself measured. A follow-up from the same laboratory used primary lung fibroblasts from a 24-week fetus that stopped dividing at passage 34, the Hayflick limit for that culture, with shortened telomeres relative to early passage. Adding Epithalon to the aging culture was reported to restore telomere length to roughly the early-passage size and let the exposed cells complete 10 further divisions, to passage 44, while still dividing, against a control that stopped at passage 34. Both of those are single-laboratory, cell-culture findings with no organism-level lifespan measured. In 2025, a laboratory with no connection to the original group, at Brunel University London, independently tested Epithalon on 2 breast cancer cell lines (21NT, BT474) and 2 normal human cell lines (IBR.3 fibroblasts, HMEC mammary epithelial cells). It reported telomere lengthening and higher hTERT gene expression in all 4 lines, but by different routes: in the 2 cancer lines, telomerase enzyme activity itself did not rise significantly despite the higher hTERT message, and telomere lengthening tracked instead with a large rise in ALT activity, an alternative, telomerase-independent lengthening pathway associated with some cancers; in the 2 normal cell lines, telomerase enzyme activity itself rose substantially and ALT activity barely moved. The normal cells needed 3 weeks of exposure to show a significant telomere-length change, versus 4 days in the cancer lines. That paper is the first independent replication located of any part of the telomerase story, and it also complicates the original story by showing the effect runs through different mechanisms in normal versus cancerous cells. A formal correction was published 2 months after the original paper stating that the wrong versions of Figures 1, 2 and 3 had appeared; the correction replaces those figures but does not state in its own text whether any numeric value or direction of effect changed, so specific fold-change figures from that paper should be regarded as approximate pending independent confirmation against the corrected figures. None of this is organism-level lifespan data, and none of it was measured on Epithalamin, the extract. IN VITRO in vitro, human fetal-derived fibroblast cultures for the original 2003 to 2004 work; in vitro, 2 human breast cancer lines and 2 normal human cell lines for the independent 2025 replication Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Telomerase activity and telomere length in human cell lines

   In telomerase-negative human fetal fibroblasts grown in culture, adding Epithalon was reported to induce expression of the telomerase catalytic subunit, measurable telomerase enzymatic activity, and telomere elongation; the authors read that as reactivation of the telomerase gene and proposed it could extend the lifespan of a cell population, a step beyond what the experiment itself measured. A follow-up from the same laboratory used primary lung fibroblasts from a 24-week fetus that stopped dividing at passage 34, the Hayflick limit for that culture, with shortened telomeres relative to early passage. Adding Epithalon to the aging culture was reported to restore telomere length to roughly the early-passage size and let the exposed cells complete 10 further divisions, to passage 44, while still dividing, against a control that stopped at passage 34. Both of those are single-laboratory, cell-culture findings with no organism-level lifespan measured. In 2025, a laboratory with no connection to the original group, at Brunel University London, independently tested Epithalon on 2 breast cancer cell lines (21NT, BT474) and 2 normal human cell lines (IBR.3 fibroblasts, HMEC mammary epithelial cells). It reported telomere lengthening and higher hTERT gene expression in all 4 lines, but by different routes: in the 2 cancer lines, telomerase enzyme activity itself did not rise significantly despite the higher hTERT message, and telomere lengthening tracked instead with a large rise in ALT activity, an alternative, telomerase-independent lengthening pathway associated with some cancers; in the 2 normal cell lines, telomerase enzyme activity itself rose substantially and ALT activity barely moved. The normal cells needed 3 weeks of exposure to show a significant telomere-length change, versus 4 days in the cancer lines. That paper is the first independent replication located of any part of the telomerase story, and it also complicates the original story by showing the effect runs through different mechanisms in normal versus cancerous cells. A formal correction was published 2 months after the original paper stating that the wrong versions of Figures 1, 2 and 3 had appeared; the correction replaces those figures but does not state in its own text whether any numeric value or direction of effect changed, so specific fold-change figures from that paper should be regarded as approximate pending independent confirmation against the corrected figures. None of this is organism-level lifespan data, and none of it was measured on Epithalamin, the extract.^{References 1, 2, 3, 4}

   Modelin vitro, human fetal-derived fibroblast cultures for the original 2003 to 2004 work; in vitro, 2 human breast cancer lines and 2 normal human cell lines for the independent 2025 replication

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Khavinson VKh, Bondarev IE, Butyugov AA. Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells. Bull Exp Biol Med. 2003;135(6):590-592. PMID 12937682, DOI 10.1023/a:1025493705728. Khavinson VKh, Bondarev IE, Butyugov AA, Smirnova TD. Peptide promotes overcoming of the division limit in human somatic cell. Bull Exp Biol Med. 2004;137(5):503-506. PMID 15455129, DOI 10.1023/b:bebm.0000038164.49947.8c. Al-Dulaimi S, Thomas R, Matta S, Roberts T. Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;26(5):178. PMID 40908429, DOI 10.1007/s10522-025-10315-x, with a published correction: Correction: Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. Biogerontology. 2025;27(1):1. PMID 41240216, DOI 10.1007/s10522-025-10326-8.

   PubMed 12937682 PubMed 15455129 PubMed 40908429 PubMed 41240216

   How this citation was checked

   PubMed esummary and efetch were queried live on this pass for PMIDs 12937682, 15455129, 40908429 and 41240216, and Crossref was queried live for all 4 DOIs; author order, journal, year, volume, issue and pages all matched across both sources for every record. The 12937682 abstract states verbatim that Epithalon 'induced expression of the catalytical subunit, enzymatic activity of telomerase, and telomere elongation' and that this indicates 'the possibility of prolonging life span of a cell population and of the whole organism'; that second clause is the authors' own extrapolation, since the experiment measured cell-culture endpoints only, which is why the finding above states the measured result and the extrapolation separately. The 15455129 abstract states the passage-34 stopping point, the restoration of telomere length, and that exposed cells 'made 10 extra divisions (44 passages) in comparison with the control and continued dividing'. For the 2025 paper, PMC was fetched live for the full text (PMC12411320) and for the correction notice (PMC12619744, dated 2025-11-15). The correction states verbatim that 'the wrong figures appeared in Figs. 1, 2 and 3' and republishes corrected versions of all 3 without its own text saying whether any reported number changed; that uncertainty is carried into the finding above rather than resolved by assumption. The PubMed abstract names the cancer lines 21NT and BT474 directly and refers to the normal-cell side only as 'normal epithelial and fibroblast cells', and it independently states the same telomerase-versus-ALT split between cancer and normal cells. The specific normal-cell-line names (IBR.3, HMEC) and the 4-day-versus-3-week exposure-duration difference appear only in the full text, not in the abstract, which is why that source distinction is drawn out rather than presenting both tiers of detail as equally abstract-level. Crossref independently confirmed the correction's DOI is a distinct, linked record from the original article's DOI, consistent with a formal published correction rather than a retraction.

2. Studied for

   Lifespan and aging-biomarker studies in mice

   2 related studies from the same core laboratory compared subcutaneous Epithalon with saline in female mice, from young adulthood until natural death, in 2 different strains, and got different results on the headline measure of mean lifespan. In outbred Swiss-derived SHR mice (54 mice per group, starting at 3 months of age, 5 consecutive days each month), Epithalon was reported to have no effect on food consumption, body weight, or mean lifespan. It was reported to slow the age-related decline of estrous cycling, reduce chromosome aberrations in bone marrow cells by 17.1%, increase the lifespan of the longest-lived 10% of animals by 13.3%, and increase maximum lifespan by 12.3%, all against the saline control. Total spontaneous tumor incidence was unchanged. In a separate strain, CBA mice (starting at 6 months of age, the same monthly schedule), Epithalon was reported to leave food consumption and physical strength unchanged while increasing body weight, increasing mean survival by 5.3%, increasing maximum lifespan by about 10 months, slowing the age-related decline of estrous cycling, and reducing body temperature, physical activity, measures of free-radical activity, and spontaneous tumor incidence. Read together rather than cherry-picked: the 2 studies agree that maximum lifespan and several aging-biomarker measures moved in a favorable direction, and disagree on mean lifespan, null in SHR mice and a reported 5.3% increase in CBA mice. That strain-to-strain inconsistency, on the single most important summary number, is stated here rather than smoothed over. Both studies share Khavinson as a senior author, and no lifespan study of Epithalon from a fully independent laboratory was located in this search pass. female mice, 2 separate strains (outbred Swiss-derived SHR and CBA), subcutaneous courses from young adulthood until natural death Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Lifespan and aging-biomarker studies in mice

   2 related studies from the same core laboratory compared subcutaneous Epithalon with saline in female mice, from young adulthood until natural death, in 2 different strains, and got different results on the headline measure of mean lifespan. In outbred Swiss-derived SHR mice (54 mice per group, starting at 3 months of age, 5 consecutive days each month), Epithalon was reported to have no effect on food consumption, body weight, or mean lifespan. It was reported to slow the age-related decline of estrous cycling, reduce chromosome aberrations in bone marrow cells by 17.1%, increase the lifespan of the longest-lived 10% of animals by 13.3%, and increase maximum lifespan by 12.3%, all against the saline control. Total spontaneous tumor incidence was unchanged. In a separate strain, CBA mice (starting at 6 months of age, the same monthly schedule), Epithalon was reported to leave food consumption and physical strength unchanged while increasing body weight, increasing mean survival by 5.3%, increasing maximum lifespan by about 10 months, slowing the age-related decline of estrous cycling, and reducing body temperature, physical activity, measures of free-radical activity, and spontaneous tumor incidence. Read together rather than cherry-picked: the 2 studies agree that maximum lifespan and several aging-biomarker measures moved in a favorable direction, and disagree on mean lifespan, null in SHR mice and a reported 5.3% increase in CBA mice. That strain-to-strain inconsistency, on the single most important summary number, is stated here rather than smoothed over. Both studies share Khavinson as a senior author, and no lifespan study of Epithalon from a fully independent laboratory was located in this search pass.^{References 5, 6}

   Modelfemale mice, 2 separate strains (outbred Swiss-derived SHR and CBA), subcutaneous courses from young adulthood until natural death

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193-202. PMID 14501183, DOI 10.1023/a:1025114230714. Anisimov VN, Khavinson VKh, Mikhalski AI, Yashin AI. Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice. Mech Ageing Dev. 2001;122(1):41-68. PMID 11163623, DOI 10.1016/s0047-6374(00)00184-6.

   PubMed 14501183 PubMed 11163623

   How this citation was checked

   PubMed esummary and efetch were queried live for both PMIDs, and Crossref was queried live on both DOIs; author order, journal, volume, issue and page range matched across both sources for both records. The 14501183 abstract, retrieved live in full, gives the group size as 54 mice and states verbatim that the peptide 'did not influence food consumption, body weight or mean life span of mice' while it 'increased by 13.3% the life span of the last 10% of the survivors (P<0.01) and by 12.3% the maximum life span', reduced chromosome aberrations 'by 17.1%, P<0.05', and left total tumor incidence unchanged. The amount figures printed in that abstract are deliberately not reproduced here, and a specific malignancy it reports reduced is deliberately not named, per the rules recorded in _render_edits. The 11163623 abstract was retrieved live and queried specifically for the pineal-tetrapeptide (Epitalon) arm as distinct from the thymic-dipeptide (Lys-Glu) arm tested in the same paper; only results attributed to the pineal-peptide arm are reported above. That abstract states the total cohort as 50 female CBA mice split across 3 arms, saline, synthetic thymic dipeptide Lys-Glu, and synthetic pineal tetrapeptide Ala-Glu-Asp-Gly, and it does not state how many mice were allocated to each individual arm; that gap is reported here rather than assumed to be an even 3-way split.

3. Studied for

   Tumor development in a transgenic mouse strain bred for early mammary tumors

   In female FVB/N mice genetically engineered to carry the HER-2/neu oncogene, a strain bred to reliably develop spontaneous mammary tumors and used in this literature as a model of accelerated aging, monthly Epithalon courses from a young age were reported to reduce the cumulative number of tumors per mouse and the maximum tumor size reached, and to lower HER-2/neu messenger RNA expression in the tumors that did form by 3.7-fold, compared with saline control mice of the same strain. A restatement of the same dataset in a second journal gives the same 3.7-fold mRNA figure and states maximum tumor size as 33% lower than control. This is a single experiment in a single transgenic mouse strain, presented in 2 venues; it describes tumor development in that specific animal model and is not a claim about any disease in a person. female FVB/N HER-2/neu transgenic mice, a single experiment restated in 2 journals Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Tumor development in a transgenic mouse strain bred for early mammary tumors

   In female FVB/N mice genetically engineered to carry the HER-2/neu oncogene, a strain bred to reliably develop spontaneous mammary tumors and used in this literature as a model of accelerated aging, monthly Epithalon courses from a young age were reported to reduce the cumulative number of tumors per mouse and the maximum tumor size reached, and to lower HER-2/neu messenger RNA expression in the tumors that did form by 3.7-fold, compared with saline control mice of the same strain. A restatement of the same dataset in a second journal gives the same 3.7-fold mRNA figure and states maximum tumor size as 33% lower than control. This is a single experiment in a single transgenic mouse strain, presented in 2 venues; it describes tumor development in that specific animal model and is not a claim about any disease in a person.^{References 7, 8}

   Modelfemale FVB/N HER-2/neu transgenic mice, a single experiment restated in 2 journals

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Anisimov VN, Khavinson VKh, Provinciali M, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Imyanitov EN, Mancini R, Franceschi C. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2002;101(1):7-10. PMID 12209581, DOI 10.1002/ijc.10570. Restated in: Anisimov VN, Khavinson VKh, Provinciali M, Mancini R, Franceschi C, et al. Epithalon inhibits tumor growth and expression of HER-2/neu oncogene in breast tumors in transgenic mice characterized by accelerated aging. Bull Exp Biol Med. 2002;133(2):167-170. PMID 12428286, DOI 10.1023/a:1015555023692.

   PubMed 12209581 PubMed 12428286

   How this citation was checked

   PubMed esummary and efetch were queried live for both PMIDs, and Crossref was queried live on both DOIs. The Crossref record for DOI 10.1002/ijc.10570 returns the full, correctly spelled Western author list: Vladimir N. Anisimov, Vladimir Kh. Khavinson, Mauro Provinciali, Irina N. Alimova, Dmitri A. Baturin, Irina G. Popovich, Mark A. Zabezhinski, Eugeni N. Imyanitov, Romina Mancini, Claudio Franceschi. PubMed's own esummary for the companion PMID 12428286 (Bulletin of Experimental Biology and Medicine, which transliterates all author names through Russian regardless of nationality) returns those same 3 Italian co-authors garbled as 'Provintsiali M, Manchini R, Francheski K'; the Crossref-verified Western spelling is used in both citation lines here rather than the transliterated PubMed version, since Provinciali and Franceschi are identifiable, independently verifiable Italian gerontology researchers and the transliteration is a known artifact of that journal's translation pipeline, not a different set of people. Both abstracts describe the same FVB/N HER-2/neu strain, the same 3.7-fold HER-2/neu mRNA reduction, and the same lead author and the same monthly schedule; the Bull Exp Biol Med abstract additionally states the 33% maximum-tumor-size figure that the Int J Cancer abstract reports only as a direction without a percentage, which is why both figures are carried above and attributed to their own source rather than merged into a single number.

4. Studied for

   Lifespan in fruit flies

   In wild-strain Drosophila melanogaster (Canton-S), Epithalon added to the culture medium only during the egg-to-larva developmental stage was reported to significantly increase the lifespan of the adult flies by 11 to 16%, at concentrations the paper describes as unprecedentedly low. The paper reports that the size of the lifespan increase did not depend on the concentration within the range tested, an unusual result worth stating plainly rather than smoothing into a typical concentration-response story. This is a single insect study from the compound's originating laboratory, with no independently replicated concentration-response relationship and no organism-level mechanism established connecting it to the telomerase work above. Drosophila melanogaster, wild-type Canton-S strain, developmental-stage-only exposure Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

   In the literature

   Lifespan in fruit flies

   In wild-strain Drosophila melanogaster (Canton-S), Epithalon added to the culture medium only during the egg-to-larva developmental stage was reported to significantly increase the lifespan of the adult flies by 11 to 16%, at concentrations the paper describes as unprecedentedly low. The paper reports that the size of the lifespan increase did not depend on the concentration within the range tested, an unusual result worth stating plainly rather than smoothing into a typical concentration-response story. This is a single insect study from the compound's originating laboratory, with no independently replicated concentration-response relationship and no organism-level mechanism established connecting it to the telomerase work above.^{References 9}

   ModelDrosophila melanogaster, wild-type Canton-S strain, developmental-stage-only exposure

   Confidence: preliminary

   A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

   Source

   Khavinson VKh, Izmaylov DM, Obukhova LK, Malinin VV. Effect of epitalon on the lifespan increase in Drosophila melanogaster. Mech Ageing Dev. 2000;120(1-3):141-149. PMID 11087911, DOI 10.1016/s0047-6374(00)00217-7.

   PubMed 11087911

   How this citation was checked

   PubMed esummary and efetch were queried live for this PMID, and Crossref was queried live on the DOI; both independently return the same author order, journal, volume, issue and page range. The retrieved abstract states the Canton-S strain, the egg-to-larva-only exposure window, the 11 to 16% lifespan increase, the paper's own characterization of the concentrations as unprecedentedly low, and that the increase did not vary across the range tested. The specific weight-percent ranges printed in that abstract are deliberately not reproduced here, so that no amount figure of any kind appears on this page.

5. Studied for

   Gene expression changes in human stem cells during neuron-like differentiation

   In human gingival mesenchymal stem cells, a cell type taken from gum tissue and capable of differentiating along several lineages, adding the AEDG peptide (Epithalon) was reported to increase the expression of 4 markers associated with differentiation toward nerve cells, Nestin, GAP43, beta-Tubulin III and Doublecortin, with reported mRNA increases in the 1.6 to 1.8-fold range. The authors propose, as a hypothesis rather than a demonstrated mechanism, that short peptides including Epithalon may act by binding chromatin-associated proteins and influencing which genes a cell's machinery can reach, and they frame the paper's own title around a 'possible epigenetic mechanism' rather than a confirmed one. This is a single study, in cells outside the body, with modest fold-changes, and it does not show that a person's nerve cells, or any other tissue, respond the same way. IN VITRO in vitro, human gingival mesenchymal stem cells Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

   In the literature

   Gene expression changes in human stem cells during neuron-like differentiation

   In human gingival mesenchymal stem cells, a cell type taken from gum tissue and capable of differentiating along several lineages, adding the AEDG peptide (Epithalon) was reported to increase the expression of 4 markers associated with differentiation toward nerve cells, Nestin, GAP43, beta-Tubulin III and Doublecortin, with reported mRNA increases in the 1.6 to 1.8-fold range. The authors propose, as a hypothesis rather than a demonstrated mechanism, that short peptides including Epithalon may act by binding chromatin-associated proteins and influencing which genes a cell's machinery can reach, and they frame the paper's own title around a 'possible epigenetic mechanism' rather than a confirmed one. This is a single study, in cells outside the body, with modest fold-changes, and it does not show that a person's nerve cells, or any other tissue, respond the same way.^{References 10}

   Modelin vitro, human gingival mesenchymal stem cells

   Confidence: preliminary

   A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

   Source

   Khavinson V, Diomede F, Mironova E, Linkova N, Trofimova S, Trubiani O, Caputi S, Sinjari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules. 2020;25(3):609. PMID 32019204, DOI 10.3390/molecules25030609.

   PubMed 32019204

   How this citation was checked

   PubMed esummary and efetch were queried live for this PMID, and Crossref was queried live on the DOI; both return the same 8 authors in the same order, Molecules, 2020, volume 25, issue 3, article 609. The abstract and retrieved text confirm the human gingival mesenchymal stem cell model, the 4 named differentiation markers, the 1.6 to 1.8-fold mRNA range, and the paper's own framing of the mechanism as possible rather than established, which is why 'possible' is retained in this dossier's own description rather than upgraded to a firm mechanism claim. This paper carries non-Khavinson-group co-authors (Diomede, Trubiani, Caputi and Sinjari, at the Universita degli Studi G. d'Annunzio Chieti-Pescara, Italy), which broadens this specific paper's provenance beyond the single-laboratory pattern that governs most of the rest of this page, though Khavinson remains first author.

6. Studied for

   Human data on Epithalamin, a different pineal material, in elderly and coronary populations

   Read the identity note first, because it governs everything in this entry: every human study located anywhere near this compound's name tested Epithalamin, the bovine pineal extract, not Epithalon, the synthetic tetrapeptide this page is about. Nothing here is evidence about Epithalon, and no effectiveness or safety conclusion carries across from either material to the other. The outcome figures these 2 papers report are also deliberately not restated on this page: they were measured on a different material, and restating human outcomes on a research-use commerce page would function as human benefit claims. What is reported here is the design. Khavinson and Morozov followed 266 elderly and older people for 6 to 8 years, giving a subset courses of Thymalin (a thymus-derived peptide preparation), Epithalamin, or both, during the first 2 to 3 years of that period, against an unspecified control group; the published abstract does not use the words randomized or blinded, and reports no confidence intervals or p-values for the ratios it gives. Separately, Korkushko and colleagues followed an elderly cardiac cohort for 15 years, with 39 people given 6 courses of Epithalamin over the first 3 years alongside standard cardiac care and 40 given standard care alone. That paper's own title describes it as a randomized comparative study, while the retrieved abstract text does not use the words blind or blinded anywhere and reports its mortality comparison only qualitatively, without a stated hazard ratio. The title also describes the preparation as coming from the pituitary gland while the abstract text attributes it to the pineal gland, an internal inconsistency in the source record that is reported here rather than silently resolved in either direction. The confidence rating on this entry describes the scale and duration of these 2 studies as human research designs, hundreds of subjects between them, multi-year, with 1 of the 2 labeled randomized. It does not describe the strength of evidence for Epithalon: because the material tested is Epithalamin, this entry supports no claim whatsoever about the synthetic peptide sold under the Epithalon name. in humans (266 elderly and older people, randomization and blinding not stated, for the pineal-and-thymus study; 39 given the extract versus 40 controls in an elderly cardiac cohort, described by that paper's own title as a randomized comparative study, with blinding not stated in the retrieved abstract text), both using Epithalamin, not Epithalon Preclinical moderate A well-described result with several independent outcome measures, but from a single laboratory or a single study design. Open for the full finding and the paper it came from.

   In the literature

   Human data on Epithalamin, a different pineal material, in elderly and coronary populations

   Read the identity note first, because it governs everything in this entry: every human study located anywhere near this compound's name tested Epithalamin, the bovine pineal extract, not Epithalon, the synthetic tetrapeptide this page is about. Nothing here is evidence about Epithalon, and no effectiveness or safety conclusion carries across from either material to the other. The outcome figures these 2 papers report are also deliberately not restated on this page: they were measured on a different material, and restating human outcomes on a research-use commerce page would function as human benefit claims. What is reported here is the design. Khavinson and Morozov followed 266 elderly and older people for 6 to 8 years, giving a subset courses of Thymalin (a thymus-derived peptide preparation), Epithalamin, or both, during the first 2 to 3 years of that period, against an unspecified control group; the published abstract does not use the words randomized or blinded, and reports no confidence intervals or p-values for the ratios it gives. Separately, Korkushko and colleagues followed an elderly cardiac cohort for 15 years, with 39 people given 6 courses of Epithalamin over the first 3 years alongside standard cardiac care and 40 given standard care alone. That paper's own title describes it as a randomized comparative study, while the retrieved abstract text does not use the words blind or blinded anywhere and reports its mortality comparison only qualitatively, without a stated hazard ratio. The title also describes the preparation as coming from the pituitary gland while the abstract text attributes it to the pineal gland, an internal inconsistency in the source record that is reported here rather than silently resolved in either direction. The confidence rating on this entry describes the scale and duration of these 2 studies as human research designs, hundreds of subjects between them, multi-year, with 1 of the 2 labeled randomized. It does not describe the strength of evidence for Epithalon: because the material tested is Epithalamin, this entry supports no claim whatsoever about the synthetic peptide sold under the Epithalon name.^{References 11, 12}

   Modelin humans (266 elderly and older people, randomization and blinding not stated, for the pineal-and-thymus study; 39 given the extract versus 40 controls in an elderly cardiac cohort, described by that paper's own title as a randomized comparative study, with blinding not stated in the retrieved abstract text), both using Epithalamin, not Epithalon

   Confidence: moderate

   A well-described result with several independent outcome measures, but from a single laboratory or a single study design.

   Source

   Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life. Neuro Endocrinol Lett. 2003;24(3-4):233-240. PMID 14523363 (no DOI found in the PubMed record or in a Crossref title and author search on this pass). Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up. Bull Exp Biol Med. 2011;151(3):366-369. PMID 22451889, DOI 10.1007/s10517-011-1332-x.

   PubMed 14523363 PubMed 22451889

   How this citation was checked

   PubMed esummary and efetch were queried live for both PMIDs. For 14523363, no DOI is present in the PubMed record and a Crossref search on the title and authors returned no matching record either, so this citation is carried by PMID only, consistent with the rule that a citation resolvable through neither PubMed nor Crossref does not go in the file; PubMed alone resolves this one. The abstract, retrieved live, states the 266-person cohort and the 6-to-8-year observation window with the preparations given during the first 2 to 3 years, and it does not contain the words randomized or blind in the retrieved text. For 22451889, Crossref was queried live on the DOI and returned the same title, authors, journal, volume, issue and pages as PubMed. The retrieved abstract text states the group sizes as 39 and 40 and the 3-year, 6-course schedule inside a 15-year follow-up, and it does not contain the words blind or blinded. The title-versus-text gland discrepancy (title says pituitary gland, abstract text calls the preparation epithalamin, 'the peptide preparation from the pineal gland') was confirmed by direct comparison of the 2 strings on this pass and is reported as an inconsistency in the source record itself, not resolved by assuming either reading is a typo: epithalamin is well established elsewhere in this literature as a pineal, not pituitary, preparation, which would argue for the abstract text over the title, but the discrepancy is stated rather than silently picking the reading that happens to be more internally consistent.

7. Studied for

   Lifespan across species with Epithalamin, the pineal extract, including in fruit flies

   Read together with the identity note above: this entry is entirely about Epithalamin, the bovine pineal extract, not Epithalon. In a single 1998 paper, the same core research group reported that Epithalamin increased mean lifespan by 11 to 31% across female Drosophila melanogaster, SHR mice, C3H/Sn mice and LIO rats, and increased both the 90th-percentile survival point and maximum lifespan in fruit flies, C3H/Sn mice and rats. Mortality rate was reported reduced 52% in fruit flies, 52% in rats and 27% in C3H/Sn mice; SHR mice showed no mortality-rate change in this account, a genuine null result inside the same paper that should not be dropped from the summary. The authors proposed increased melatonin synthesis and secretion, plus inhibition of free-radical processes, as the likely mechanism. This is the extract's own foundational cross-species paper, from the laboratory that later built the synthetic Epithalon peptide as a simplified analogue of it, and it is offered here only as background for why the extract's reputation exists, not as evidence for the peptide sold under the Epithalon name. female Drosophila melanogaster, SHR mice, C3H/Sn mice and LIO rats, all given Epithalamin, the extract Preclinical preliminary A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

   In the literature

   Lifespan across species with Epithalamin, the pineal extract, including in fruit flies

   Read together with the identity note above: this entry is entirely about Epithalamin, the bovine pineal extract, not Epithalon. In a single 1998 paper, the same core research group reported that Epithalamin increased mean lifespan by 11 to 31% across female Drosophila melanogaster, SHR mice, C3H/Sn mice and LIO rats, and increased both the 90th-percentile survival point and maximum lifespan in fruit flies, C3H/Sn mice and rats. Mortality rate was reported reduced 52% in fruit flies, 52% in rats and 27% in C3H/Sn mice; SHR mice showed no mortality-rate change in this account, a genuine null result inside the same paper that should not be dropped from the summary. The authors proposed increased melatonin synthesis and secretion, plus inhibition of free-radical processes, as the likely mechanism. This is the extract's own foundational cross-species paper, from the laboratory that later built the synthetic Epithalon peptide as a simplified analogue of it, and it is offered here only as background for why the extract's reputation exists, not as evidence for the peptide sold under the Epithalon name.^{References 13}

   Modelfemale Drosophila melanogaster, SHR mice, C3H/Sn mice and LIO rats, all given Epithalamin, the extract

   Confidence: preliminary

   A single study, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

   Source

   Anisimov VN, Mylnikov SV, Khavinson VKh. Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Ageing Dev. 1998;103(2):123-132. PMID 9701766, DOI 10.1016/s0047-6374(98)00034-7.

   PubMed 9701766

   How this citation was checked

   PubMed esummary and efetch were queried live for this PMID, and Crossref was queried live on the DOI; both independently return the same author order, journal, volume, issue and page range. The retrieved abstract confirms the 4 species and strains, the 11 to 31% mean-lifespan range, the 90th-percentile-and-maximum-lifespan increase in flies, C3H/Sn mice and rats specifically and not in SHR mice, the 52%, 52% and 27% mortality-rate reductions in flies, rats and C3H/Sn mice respectively, the explicit absence of a mortality-rate change in SHR mice, and the melatonin and free-radical mechanism proposal.

4 moderate / 3 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.