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Review
. 2022 Dec 13;19(24):16721.
doi: 10.3390/ijerph192416721.

Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis

Albert Stuart Reece  1   2 , Gary Kenneth Hulse  1   2
Affiliations
Review

Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis

Albert Stuart Reece et al. Int J Environ Res Public Health. .

Abstract

Background: Twelve separate streams of empirical data make a strong case for cannabis-induced accelerated aging including hormonal, mitochondriopathic, cardiovascular, hepatotoxic, immunological, genotoxic, epigenotoxic, disruption of chromosomal physiology, congenital anomalies, cancers including inheritable tumorigenesis, telomerase inhibition and elevated mortality.

Methods: Results from a recently published longitudinal epigenomic screen were analyzed with regard to the results of recent large epidemiological studies of the causal impacts of cannabis. We also integrate theoretical syntheses with prior studies into these combined epigenomic and epidemiological results.

Results: Cannabis dependence not only recapitulates many of the key features of aging, but is characterized by both age-defining and age-generating illnesses including immunomodulation, hepatic inflammation, many psychiatric syndromes with a neuroinflammatory basis, genotoxicity and epigenotoxicity. DNA breaks, chromosomal breakage-fusion-bridge morphologies and likely cycles, and altered intergenerational DNA methylation and disruption of both the histone and tubulin codes in the context of increased clinical congenital anomalies, cancers and heritable tumors imply widespread disruption of the genome and epigenome. Modern epigenomic clocks indicate that, in cannabis-dependent patients, cannabis advances cellular DNA methylation age by 25-30% at age 30 years. Data have implications not only for somatic but also stem cell and germ line tissues including post-fertilization zygotes. This effect is likely increases with the square of chronological age.

Conclusion: Recent epigenomic studies of cannabis exposure provide many explanations for the broad spectrum of cannabis-related teratogenicity and carcinogenicity and appear to account for many epidemiologically observed findings. Further research is indicated on the role of cannabinoids in the aging process both developmentally and longitudinally, from stem cell to germ cell to blastocystoids to embryoid bodies and beyond.

Keywords: DNA methylation; ageing; aging; cannabis; epigenotoxicity; genotoxicity; teratology.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Number of epigenomic annotations in the Schrott database for target organs by dependency status in (A) cannabis dependence and (B) withdrawal.
Figure 2
Figure 2
Significance levels (as p-values) of target organs by dependency status in (A) cannabis dependence and (B) withdrawal in the Schrott database.
Figure 3
Figure 3
(A) Numbers of gene annotations, (B) numbers of genes affected and (C) negative logarithm of p-value by cancer type—cannabis dependence Schrott data.
Figure 4
Figure 4
(A) Numbers of gene annotations, (B) numbers of genes affected and (C) negative logarithm of p-value by cancer type—cannabis withdrawal Schrott data.
Figure 5
Figure 5
Log plots of significance levels for (A) ratio of p-values between cannabis dependence and withdrawal, (B) log of the dependence/withdrawal ratio of total gene numbers affected between cannabis dependence and withdrawal and (C) log of the withdrawal/dependence ratio of total gene numbers affected between cannabis dependence and withdrawal; each by tumor type from the Schrott EWAS data.
See this image and copyright information in PMC

References

    1. Lopez-Otin C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–1217. doi: 10.1016/j.cell.2013.05.039. - DOI - PMC - PubMed
    1. Yilmaz D., Furst A., Meaburn K., Lezaja A., Wen Y., Altmeyer M., Reina-San-Martin B., Soutoglou E. Activation of homologous recombination in G1 preserves centromeric integrity. Nature. 2021;600:748–753. doi: 10.1038/s41586-021-04200-z. - DOI - PubMed
    1. Franceschi C., Bonafe M., Valensin S., Olivieri F., De Luca M., Ottaviani E., De Benedictis G. Inflamm-aging: An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 2000;908:244–254. doi: 10.1111/j.1749-6632.2000.tb06651.x. - DOI - PubMed
    1. Salvioli S., Monti D., Lanzarini C., Conte M., Pirazzini C., Bacalini M.G., Garagnani P., Giuliani C., Fontanesi E., Ostan R., et al. Immune system, cell senescence, aging and longevity--inflamm-aging reappraised. Curr. Pharm. Des. 2013;19:1675–1679. - PubMed
    1. Beausejour C.M., Campisi J. Ageing: Balancing regeneration and cancer. Nature. 2006;443:404–405. doi: 10.1038/nature05221. - DOI - PubMed