The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging
Studies indicate that psilocybin has beneficial effects on neuronal processes and that it facilitates neurogenesis. The 5-HT (serotonin) system is one of the primary targets of psilocybin.
Raval, N. R., Johansen, A., Donovan, L. L., Ros, N. F., Ozenne, B., Hansen, H. D., & Knudsen, G. M. (2021). A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms22020835
de Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021). Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. In Frontiers in Psychiatry. https://doi.org/10.3389/fpsyt.2021.724606
Aleksandrova, L. R., & Phillips, A. G. (2021). Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. In Trends in Pharmacological Sciences. https://doi.org/10.1016/j.tips.2021.08.003
Inserra, A., De Gregorio, D., & Gobbi, G. (2021). Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms. Pharmacological Reviews. https://doi.org/10.1124/PHARMREV.120.000056
Data confirms that psilocybin enhances emotional well-being in a longitudinal manner. Furthermore, numerous brain-imaging studies concluded that psilocybin improves cognitive processes associated with empathy and prosocial behaviour.
Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. L. (2018). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2017.12.041
Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenweider, F. X. (2015). Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2014.04.010
Grimm, O., Kraehenmann, R., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2018). Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination. European Neuropsychopharmacology. https://doi.org/10.1016/j.euroneuro.2018.03.016
Recent research supports the notion that psilocybin & DMT have anti-inflammatory effects and that these substances may modulate the immune-system. There is a lot of room for new findings. For instance, the novel "psilocybin-microbiome hypothesis" (Germann, 2021) predicts that psilocybin changes the genetic variation of the human microbiome in a systematic quantifiable fashion.
Lee, S. H., Yoon, S. H., Jung, Y., Kim, N., Min, U., Chun, J., & Choi, I. (2020). Emotional well-being and gut microbiome profiles by enterotype. Scientific Reports. https://doi.org/10.1038/s41598-020-77673-z
Qamar, N., Castano, D., Patt, C., Chu, T., Cottrell, J., & Chang, S. L. (2019). Meta-analysis of alcohol induced gut dysbiosis and the resulting behavioral impact. Behavioural Brain Research, 376, 112196. https://doi.org/10.1016/j.bbr.2019.112196
Sarkar, A., Harty, S., Johnson, K. V. A., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020). The role of the microbiome in the neurobiology of social behaviour. Biological Reviews. https://doi.org/10.1111/brv.12603
Source: Tullis, P. (2021). How ecstasy and psilocybin are shaking up psychiatry. Nature. https://doi.org/10.1038/d41586-021-00187-9
A plethora of genetic and geroscience studies indicate that telomere length is a reliable biomarker of cellular aging [1,2], i.e., telomeres are regarded as a robust indicator of mitotic cell and possibly organismal longevity . Attrition/uncapping of telomeres is associated with the degeneration of multiple systems such as various organ failures, de- pletion of the totipotent stem cell répertoire, tissue atrophy, impairments in injury responses and various (neuro)restorative processes, inter alia . Furthermore, it has been proposed that telomeres function as a “psychobiomarker” as they are partially regulated by psychological factors [5,6].
Germann, C. B. (2020). The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging. Medical Hypotheses, 134, 109406. https://doi.org/10.1016/j.mehy.2019.109406
Telomere image source:
U.S. Department of Energy Genomic Science program
Medical Hypotheses, 134, 1–9.
UCTV [ID: 23204] [Recorded on 11/10/2011] [Health and Medicine]
- Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., … Nutt, D. J. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports, 7(1), 13187. https://doi.org/10.1038/s41598-017-13282-7
- Catlow, B. J., Song, S., Paredes, D. A., Kirstein, C. L., & Sanchez-Ramos, J. (2013). Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Experimental Brain Research, 228(4), 481–491. https://doi.org/10.1007/s00221-013-3579-0
- Epel, E., Daubenmier, J., Moskowitz, J. T., Folkman, S., & Blackburn, E. (2009). Can Meditation Slow Rate of Cellular Aging? Cognitive Stress, Mindfulness, and Telomeres. Annals of the New York Academy of Sciences, 1172(1), 34–53. https://doi.org/10.1111/j.1749-6632.2009.04414.x
- Gotlib, I. H., LeMoult, J., Colich, N. L., Foland-Ross, L. C., Hallmayer, J., Joormann, J., … Wolkowitz, O. M. (2015). Telomere length and cortisol reactivity in children of depressed mothers. Molecular Psychiatry, 20(5), 615–620. https://doi.org/10.1038/mp.2014.119
- Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268–283. https://doi.org/10.1007/s00213-006-0457-5
- Hoge, E. A., Chen, M. M., Orr, E., Metcalf, C. A., Fischer, L. E., Pollack, M. H., … Simon, N. M. (2013). Loving-Kindness Meditation practice associated with longer telomeres in women. Brain, Behavior, and Immunity, 32, 159–163. https://doi.org/10.1016/j.bbi.2013.04.005
- Johnson, M. W., & Griffiths, R. R. (2017). Potential Therapeutic Effects of Psilocybin. Neurotherapeutics, 14(3), 734–740. https://doi.org/10.1007/s13311-017-0542-y
- Kraehenmann, R., Schmidt, A., Friston, K., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2016). The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. NeuroImage: Clinical, 11, 53–60. https://doi.org/10.1016/j.nicl.2015.08.009
- Malan, S., Hemmings, S., Kidd, M., Martin, L., & Seedat, S. (2011). Investigation of telomere length and psychological stress in rape victims. Depression and Anxiety, 28(12), 1081–1085. https://doi.org/10.1002/da.20903
- McCorvy, J. D., Olsen, R. H., & Roth, B. L. (2016). Psilocybin for depression and anxiety associated with life-threatening illnesses. Journal of Psychopharmacology, 30(12), 1209–1210. https://doi.org/10.1177/0269881116675771
- Preller, K. H., Pokorny, T., Krähenmann, R., Dziobek, I., Stämpfli, P., & Vollenweider, F. X. (2015). The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making. European Psychiatry, 30, 22. https://doi.org/10.1016/S0924-9338(15)30017-1
- Roseman, L., Demetriou, L., Wall, M. B., Nutt, D. J., & Carhart-Harris, R. L. (2018). Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology, 142, 263–269. https://doi.org/10.1016/j.neuropharm.2017.12.041
- Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., … Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165–1180. https://doi.org/10.1177/0269881116675512
- Wei, Y. Bin, Backlund, L., Wegener, G., Mathé, A. A., & Lavebratt, C. (2015). Telomerase dysregulation in the hippocampus of a rat model of depression: Normalization by lithium. International Journal of Neuropsychopharmacology. https://doi.org/10.1093/ijnp/pyv002
- Wikgren, M., Maripuu, M., Karlsson, T., Nordfjäll, K., Bergdahl, J., Hultdin, J., … Norrback, K.-F. (2012). Short Telomeres in Depression and the General Population Are Associated with a Hypocortisolemic State. Biological Psychiatry, 71(4), 294–300. https://doi.org/10.1016/j.biopsych.2011.09.015
- Wolkowitz, O. M., Mellon, S. H., Epel, E. S., Lin, J., Dhabhar, F. S., Su, Y., … Blackburn, E. H. (2011). Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings. PLoS ONE, 6(3), e17837. https://doi.org/10.1371/journal.pone.0017837
- Wolkowitz, O. M., Reus, V. I., & Mellon, S. H. (2011). Telomere shortening in leukocyte subpopulations in depression. Dialogues in Clinical Neuroscience, 13(1), 25–39. https://doi.org/10.1186/1471-244X-14-192
- Wolkowitz, O. M., Reus, V. I., & Mellon, S. H. (2011). Of sound mind and body: depression, disease, and accelerated aging. Dialogues in Clinical Neuroscience, 13(1), 25–39. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21485744
“Those who have handled sciences have been either men of experiment or men of dogmas. The men of experiment are like the ant, they only collect and use; the reasoners resemble spiders, who make cobwebs out of their own substance. But the bee takes a middle course: it gathers its material from the flowers of the garden and of the field, but transforms and digests it by a power of its own. Not unlike this is the true business of philosophy; for it neither relies solely or chiefly on the powers of the mind, nor does it take the matter which it gathers from natural history and mechanical experiments and lay it up in the memory whole, as it finds it, but lays it up in the understanding altered and digested. Therefore from a closer and purer league between these two faculties, the experimental and the rational (such as has never yet been made), much may be hoped.”
Francis Bacon, Novum Oganum, Book I (1620)
A biological analogy by Sir Francis Bacon (Novum Organum, 1620)
N.B. Under construction... May contain errors!
Arthur Heffter isolates mescaline
He isolated mescaline from the peyote cactus in 1897, the first such isolation of a naturally occurring psychedelic substance in pure form. In addition, he conducted experiments on its effects by comparing the effects of peyote and mescaline on himself.
Heffter, the first Chairman of the German Society of Pharmacology, was responsible for isolating mescaline as the active psychedelic component from the peyote cactus, thereby initiating a series of studies along with an Institute that, much like the Handbook and the discipline of pharmacology, continues to discover and disseminate new findings to this day. These early endeavors to establish pharmacology as a viable and valuable contributor to the medical sciences met with considerable resistance and challenges. However, the persistence and dedication of these early pharmacologists placed pharmacology on a firm foundation from which to spread this discipline globally, leading ultimately to our current understanding of the principles of drug action and with an impact likely unanticipated by these founding scientists.1894). Ueber Pellote - Ein Beitrag zur pharmakologischen Kenntniss der Cacteen. Archiv Für Experimentelle Pathologie Und Pharmakologie. (
Plain numerical DOI: 10.1007/BF01864855
Albert Hofmann (1906–2008) discovered LSD in 1938, but he was
unaware of its psychoactivity until 1943 when he conducted the first self-
experiment. Hofmann, who later served as a member of the Nobel Prize
Committee, stated on his 100th birthday: “It gave me an inner joy, an open
mindedness, a gratefulness, open eyes and an internal sensitivity for the mir-
acles of creation. [...] I think that in human evolution it has never been as
necessary to have this substance LSD. It is just a tool to turn us into what
we are supposed to be."
1959 Hofmann isoltes psilocybin
Hofmann, A., & Troxler, F. (1959). Identifizierung von Psilocin.
Experientia, 15(3), 101–102.
Hofmann, A., Frey, A., Ott, H., Petrzilka, T., & Troxler, F. (1958a).
Elucidation of the structure and the synthesis of psilocybin.
Experientia, 14(11), 397–399.
Hofmann, A., Heim, R., Brack, A., & Kobel, H. (1958b). Psilocybin, ein
psychotroper Wirkstoff aus dem mexikanischen Rauschpilz
Psilocybe mexicana Heim. Experientia.
Hofmann, A., Heim, R., Brack, A., Kobel, H., Frey, H., Ott, H., ...
Troxler, F. (1959). Psilocybin und Psilocin, zwei psychotrope
Wirkstoffe aus mexikanischen Rauschpilzen. Helvetica Chimica
Acta, 42, 1557–1572.
Nixons \\\\\\\"War on drugs\\\\\\\"
Controlled Substances Act
President Richard M. Nixon signed the Controlled Substances Act (CSA) into law in 1970. This statute calls for the regulation of certain drugs and substances.
The CSA outlines five “schedules” used to classify drugs based on their medical application and potential for abuse.
Schedule 1 drugs are considered the most dangerous, as they pose a very high risk for addiction with little evidence of medical benefits. Marijuana, LSD, heroin, MDMA (ecstasy) and other drugs are included on the list of Schedule 1 drugs.
The substances considered least likely to be addictive, such as cough medications with small amounts of codeine, fall into the Schedule 5 category.
Nixon and the War on Drugs
In June 1971, Nixon officially declared a “War on Drugs,” stating that drug abuse was “public enemy number one.
John Daniel Ehrlichman who was at this time Assistant to the President (for Domestic Affairs) stated in an interview in 1994 (published in “Harpers”in 2016): “The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I’m saying? We knew we could not make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did."
Maintaining a healthy lifestyle is challenging at any age, and for adults 50 and over, one of the best ways to combat the symptoms of “old age” is to be educated about ways to stay healthy.
In a nutshell, this hypothesis postulates that psilocybin slows down genetic ageing. This effect can be measured quantitatively via modern molecular methods such as telomere analysis or epigenetic clock analysis.
"The exciting discovery that telomere shortening is associated with many health conditions, and that telomere lengths can be altered in response to social and environmental exposures, has underscored the need for methods to accurately and consistently quantify telomere length.
The purpose of this paper is to provide a comprehensive summary that compares and contrasts the current technologies used to assess telomere length."
An epigenetic clock is a biochemical test that can be used to measure age. The test is based on DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules.
3 major epigenetic clocks:
a) telomere length
b) p16INK4a expression levels (also known as INK4a/ARF locus)
c) microsatellite mutations
Telomere & telomerase analysis
Abstract: The terminal chromatin structures at the ends of eukaryotic chromosomes, the telomeres, are a focus of intensive research due to their importance for the maintenance of chromosome integrity. Their shortening due to incomplete replication functions as a molecular clock counting the number of cell divisions, and ultimately results in cell-cycle arrest and cellular senescence. Telomere shortening can be compensated by the nucleoprotein enzyme complex called telomerase, which is able to extend shortened telomeres. In humans, only embryonic and germ cells show telomerase activity that is sufficient for telomere length stability and cellular immortality. Unfortunately, telomerase is activated in cancer cells, which, thus, achieve unlimited growth and a malignant phenotype. Even if there were no any other links of telomere biology to other essential processes in the cell nucleus such as DNA repair, chromosome positioning, and nuclear architecture in mitosis and meiosis, the close connection of telomere biology to aging and cancer makes telomeres and techniques for their analysis important enough from the point of view of us, mortal and disease-prone people. In this chapter, we describe the most common types of analyses used in telomere biology: screening for typical and variant telomeric sequences, determination of telomere lengths, and measurement of telomerase activity. © 2008 Humana Press.
Fajkus, J., Dvořáčková, M., & Sýkorová, E. (2008). Analysis of telomeres and telomerase. Methods in Molecular Biology. https://doi.org/10.1007/978-1-59745-406-3_17
Telomere Length and All-Cause Mortality: A Meta-analysis
Telomere attrition is associated with increased morbidity and mortality of various age-related diseases. Reports of association between telomere length (TL) and all-cause mortality remain inconsistent. In the present study, a meta-analysis was performed using published cohort studies and un-published data from the Swedish Twin Registry (STR). Twenty-five studies were included: four STR cohorts (12,083 individuals with 2517 deaths) and 21 published studies. In the STR studies, one standard deviation (SD) decrement of leukocyte TL corresponded to 13% increased all-cause mortality risk (95% confidence interval [CI]: 7%–19%); individuals in the shortest TL quarter had 44% higher hazard (95% CI: 27%–63%) than those in the longest quarter. Meta-analysis of all eligible studies (121,749 individuals with 21,763 deaths) revealed one SD TL decrement-associated hazard ratio of 1.09 (95% CI: 1.06–1.13); those in the shortest TL quarter had 26% higher hazard (95% CI: 15%–38%) compared to the longest quarter, although between-study heterogeneity was observed. Analyses stratified by age indicated that the hazard ratio was smaller in individuals over 80 years old. In summary, short telomeres are associated with increased all-cause mortality risk in the general population. However, TL measurement techniques and age at measurement contribute to the heterogeneity of effect estimation.
Wang, Q., Zhan, Y., Pedersen, N. L., Fang, F., & Hägg, S. (2018). Telomere Length and All-Cause Mortality: A Meta-analysis. In Ageing Research Reviews. https://doi.org/10.1016/j.arr.2018.09.002
Psilocybin reduces depression (meta-analysis)
Abstract: The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges’ gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.
Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. In Psychiatry Research. https://doi.org/10.1016/j.psychres.2020.112749
Background: Classical psychedelics are a group of drugs which act as agonists on the serotonin-2A (5-HT2A) receptor. Evidence suggests they may have a uniquely rapid and enduring positive effect on mood. However, marked heterogeneity between methodological designs in this emerging field remains a significant concern. Aims: To determine how differences in the type of psychedelic agent used and the number of dosing sessions administered affect subjects’ depression and anxiety outcomes and adverse drug reactions (ADR). Methods: This review collected and screened 1591 records from the MEDLINE and Web of Science databases for clinical trials reporting objective data on mood for subjects with a known anxiety or depression. Results: After screening, nine clinical trials met inclusion criteria. Meta-analysis of these studies showed significant, large positive effect sizes for measures of anxiety (Cohen’s d = 1.26) and depression (Cohen’s d = 1.38) overall. These positive effects were also significant at acute (⩽1 week) and extended (>1 week) time points. No significant differences were observed between trials using different psychedelic agents (psilocybin, ayahuasca or lysergic acid diethylamide (LSD)), however, a significant difference was observed in favour of trials with multiple dosing sessions. No serious ADR were reported. Conclusion: Psilocybin, ayahuasca and LSD all appear to be effective and relatively safe agents capable of producing rapid and sustained improvements in anxiety and depression. Moreover, the findings of the present analysis suggest that they may show a greater efficacy when given to patients over multiple sessions as compared to the more common single session used in many of the existing trials.
Leger, R. F., & Unterwald, E. M. (2021). Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis. In Journal of Psychopharmacology. https://doi.org/10.1177/02698811211044688
Depression & telomere length
Background: Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association. Methods Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model. Results Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohen's d effect size of -0.205 (p
Ridout, K. K., Ridout, S. J., Price, L. H., Sen, S., & Tyrka, A. R. (2016). Depression and telomere length: A meta-analysis. Journal of Affective Disorders. https://doi.org/10.1016/j.jad.2015.11.052
Tracking the Epigenetic Clock Across the Human Life Course: A Meta-analysis of Longitudinal Cohort Data
Background: Epigenetic clocks based on DNA methylation yield high correlations with chronological age in cross-sectional data. Due to a paucity of longitudinal data, it is not known how Δ age (epigenetic age-chronological age) changes over time or if it remains constant from childhood to old age. Here, we investigate this using longitudinal DNA methylation data from five datasets, covering most of the human life course. Methods Two measures of the epigenetic clock (Hannum and Horvath) are used to calculate Δ age in the following cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) offspring (n = 986, total age-range 7-19 years, 2 waves), ALSPAC mothers (n = 982, 16-60 years, 2 waves), InCHIANTI (n = 460, 21-100 years, 2 waves), SATSA (n = 373, 48-99 years, 5 waves), Lothian Birth Cohort 1936 (n = 1,054, 70-76 years, 3 waves), and Lothian Birth Cohort 1921 (n = 476, 79-90 years, 3 waves). Linear mixed models were used to track longitudinal change in Δ age within each cohort. Results For both epigenetic age measures, Δ age showed a declining trend in almost all of the cohorts. The correlation between Δ age across waves ranged from 0.22 to 0.82 for Horvath and 0.25 to 0.71 for Hannum, with stronger associations in samples collected closer in time. Conclusions Epigenetic age increases at a slower rate than chronological age across the life course, especially in the oldest population. Some of the effect is likely driven by survival bias, where healthy individuals are those maintained within a longitudinal study, although other factors like the age distribution of the underlying training population may also have influenced this trend.
Marioni, R. E., Suderman, M., Chen, B. H., Horvath, S., Bandinelli, S., Morris, T., Beck, S., Ferrucci, L., Pedersen, N. L., Relton, C. L., Deary, I. J., & Hägg, S. (2019). Tracking the epigenetic clock across the human life course: A meta-analysis of longitudinal cohort data. Journals of Gerontology - Series A Biological Sciences and Medical Sciences. https://doi.org/10.1093/gerona/gly060
Meditation & telomere length
Objective: Telomeres are the caps at the end of chromosomes. Short telomeres are a biomarker for worsening health and early death. Design: The present study consolidated research on meditation and telomere length through a meta-analysis of results of studies examining the effect of meditation on telomere length by comparing the telomere length of meditating participants with participants in control conditions. Results: A search of the literature identified 11 studies reporting 12 comparisons of meditating individuals with individuals in control conditions. An overall significant weighted effect size of g =.40 indicated that the individuals in meditation conditions had longer telomeres. When an outlier effect size was trimmed from the analysis, the effect size was smaller, g =.16. Across studies, a greater number of hours of meditation among participants in meditation conditions was associated with larger effect sizes. Conclusion: These findings provide tentative support for the hypothesis that participants in meditation conditions have longer telomeres than participants in comparison conditions, and that a greater number of hours of meditation is associated with a greater impact on telomere biology. The results of the meta-analysis have potential clinical significance in that they suggest that meditation-based interventions may prevent telomere attrition or increase telomere length.
Schutte, N. S., Malouff, J. M., & Keng, S. L. (2020). Meditation and telomere length: a meta-analysis. Psychology and Health. https://doi.org/10.1080/08870446.2019.1707827
Epigenetic clock analysis
Abstract: Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epi genetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti. Extrinsic epigenetic age acceleration (EEAA) exhibits significant associations with fish intake (p=0.02), moderate alcohol consumption (p=0.01), education (p=3x10-5), BMI (p=0.01), and blood carotenoid levels (p=1x10-5)-an indicator of fruit and vegetable consumption, whereas intrinsic epigenetic age acceleration (IEAA) is associated with poultry intake (p=0.03) and BMI (p=0.05). Both EEAA and IEAA were also found to relate to indicators of metabolic syndrome, which appear to mediate their associations with BMI. Metformin-the first-line medication for the treatment of type 2 diabetes-does not delay epigenetic aging in this observational study. Finally, longitudinal data suggests that an increase in BMI is associated with increase in both EEAA and IEAA. Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity, and education, as well as the health risks of obesity and metabolic syndrome.
Quach, A., Levine, M. E., Tanaka, T., Lu, A. T., Chen, B. H., Ferrucci, L., Ritz, B., Bandinelli, S., Neuhouser, M. L., Beasley, J. M., Snetselaar, L., Wallace, R. B., Tsao, P. S., Absher, D., Assimes, T. L., Stewart, J. D., Li, Y., Hou, L., Baccarelli, A. A., … Horvath, S. (2017). Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging, 9(2), 419–446. https://doi.org/10.18632/aging.101168
Horvath's epigenetic clock
Abstract: Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: Why do we age?
Horvath, S., & Raj, K. (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature Reviews Genetics, 19(6), 371–384. https://doi.org/10.1038/s41576-018-0004-3
The epigenetic "meta-clock"
Underlying features of epigenetic aging clocks in vivo and in vitro
Abstract: Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi-omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi-omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging-cellular senescence and mitochondrial dysfunction. Finally, using multi-tissue data to deconstruct the epigenetic clock signals, we developed a meta-clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks.
Liu, Z., Leung, D., Thrush, K., Zhao, W., Ratliff, S., Tanaka, T., Schmitz, L. L., Smith, J. A., Ferrucci, L., & Levine, M. E. (2020). Underlying features of epigenetic aging clocks in vivo and in vitro. Aging cell, 19(10), e13229. https://doi.org/10.1111/acel.13229
Comparative analysis for 11 epigenetic clocks
"We compared 11 existing epigenetic clocks on the basis of their functional characteristics, transcriptional associations, and ability to capture hallmarks of aging. We then decomposed their signals and recombined them into a “meta‐clock.” This meta‐clock showed stronger prediction of all‐cause mortality than any one epigenetic clock and was able to distinguish tumor from normal tissue and capture epigenetic changes in two types of senescence (replicative and oncogene induced)."
Epigenetic clock analysis in long-term meditators
In this paper, we examined whether meditation practice influences the epigenetic clock, a strong and reproducible biomarker of biological aging, which is accelerated by cumulative lifetime stress and with age-related chronic diseases. Using the Illumina 450 K array platform, we analyzed the DNA methylome from blood cells of long-term meditators and meditation-naïve controls to estimate their Intrinsic Epigenetic Age Acceleration (IEAA), using Horvath's calculator. IEAA was similar in both groups. However, controls showed a different IEAA trajectory with aging than meditators: older controls (age ≥ 52) had significantly higher IEAAs compared with younger controls (age
Chaix, R., Alvarez-López, M. J., Fagny, M., Lemee, L., Regnault, B., Davidson, R. J., Lutz, A., & Kaliman, P. (2017). Epigenetic clock analysis in long-term meditators.
Recent experimental evidence supports the notion that psilocybin has modeulatory efefcts on gene expression.
For instance, psilocybin produces an immunology-related genetic response in the prefrontal cortex of pig brains.
- Pigs respond to 0.08 mg/kg psilocybin i.v. with headshakes, scratching and rubbing behaviour.
- A similar dose produce a cerebral 5-HT2A receptor occupancy of ~67%.
- 1 week after psilocybin exposure an immunology-related genetic response was seen in prefrontal cortex.
Abstract: Psilocybin has in some studies shown promise as treatment of major depressive disorder and psilocybin therapy was in 2019 twice designated as breakthrough therapy by the U.S. Food and Drug Administration (FDA). A very particular feature is that ingestion of just a single dose of psilocybin is associated with lasting changes in personality and mood. The underlying molecular mechanism behind its effect is, however, unknown. In a translational pig model, we here present the effects of a single dose of psilocybin on pig behaviour, receptor occupancy and gene expression in the brain. An acute i.v. injection of 0.08 mg/kg psilocybin to awake female pigs induced characteristic behavioural changes in terms of headshakes, scratching and rubbing, lasting around 20 min. A similar dose was associated with a cerebral 5-HT2A receptor occupancy of 67%, as determined by positron emission tomography, and plasma psilocin levels were comparable to what in humans is associated with an intense psychedelic experience. We found that 19 genes were differentially expressed in prefrontal cortex one day after psilocybin injection, and 3 genes after 1 week. Gene Set Enrichment Analysis demonstrated that multiple immunological pathways were regulated 1 week after psilocybin exposure. This provides a framework for future investigations of the lasting molecular mechanisms induced by a single dose of psilocybin. In the light of an ongoing debate as to whether psilocybin is a safe treatment for depression and other mental illnesses, it is reassuring that our data suggest that any effects on gene expression are very modest.
Donovan, L. L., Johansen, J. V., Ros, N. F., Jaberi, E., Linnet, K., Johansen, S. S., Ozenne, B., Issazadeh-Navikas, S., Hansen, H. D., & Knudsen, G. M. (2021). Effects of a single dose of psilocybin on behaviour, brain 5-HT2A receptor occupancy and gene expression in the pig. European Neuropsychopharmacology. https://doi.org/10.1016/j.euroneuro.2020.11.013
Fughi (adaptogens) play a major role in TCM and they have a wide range of systemic effects.
cf. Reishi babies
cf. Turkey Tail
Holgenome theory of evolution
Cell-division and apoptosis
Psilocybin enhances creativity. This increase in creativity then enhances research on psilocybin and creativity. It is thus a cybernetic loop which iteratively feeds back into itself. Given that psilocybin increases self-awareness, the psychological sciences can benefit enormously from insights derived from this field of iquiery. A more mature psychology is beneficial to all levels of existence, from the material to the spiritual.
Here you can find new ideas & memes focusing on psilocybin and related topics.
A moonshot, in a scientific context, is an exploratory and highly ambitious endevour which charts novel teritory. It is an investment of time and recourses with a very low a priori likelihood of sucess or quantifiable profitability. This methodolgy of innovation is an adoptation of a quasi-evolutionary approach towards memetics. It promotes creativity and novel thinking outside the dominant paradigm.
"... there is no more rational procedure than the method of trial and error – of conjecture and refutation: of boldly proposing theories; of trying our best to show that these are erroneous; and of accepting them tentatively if our critical efforts are unsuccessful. From the point of view here developed, all laws, all theories, remain essentially tentative, or conjectural, or hypothetical, even when we feel unable to doubt them any longer."
Sir Karl Popper, British Council lecture given at Peterhouse, Cambridge, in Summer 1953. Published under the title "Philosophy of Science: a Personal Report" in C. A. Mace (ed.), British Philosophy in Mid-Century: a Cambridge Symposium. London: Allen & Unwin, 1966