How bad is accelerated senescence in consumers of drugs of abuse?
DOI:
https://doi.org/10.20882/adicciones.236Keywords:
Drugs of abuse, senescence, mitochondrial DNA, stem/progenitor cell proliferation, lipofuscinAbstract
The aging or senescence process that follows maturation is characterized by time-related functional decline due to genetic, biochemical, physiological and anatomical degeneration in tissues and organ systems with time. Oxidative damage to mitochondrial DNA (mtDNA) in the heart and brain is inversely related to maximum life span of mammals, suggesting that accumulation of mtDNA damage is involved in the various disorders associated with aging, cancer and neurodegeneration. The suppression of stem/progenitor cell proliferation also contributes to the aging process, by reducing tissue regeneration and repair and ultimately reducing longevity. Another important factor is the intracellular deposition of lipofuscin granules (age pigment), a non-degradable polymeric material accumulated within lysosomes, which ultimately exacerbate oxidative stress levels in senescent cells. Drugs of abuse can strongly contribute to these senescence accelerating factors in the brain. Methylenedioxymethamphetamine (“ecstasy”) and methamphetamine were shown to promote deletions in brain mtDNA. Concerning stem/ progenitor cells, it has been shown that several opiates and psychostimulants, including ecstasy, decrease the self-renewal capacity of the hippocampus by diminishing the rate of proliferation of neural progenitors and/or by impairing the long-term survival of neural precursors. Chronic alcohol consumption induces lipofuscin deposition in neurons and heart cells. These facts provide interesting hints on the potential of these drugs in accelerating brain senescence. While the extent and severity of the contribution of drugs of abuse for accelerated senescence remain uncertain, these putative aging effects add up to the dark side of drug addiction and undoubtedly require a strong research effort in the near future.References
Aberg, E., Hofstetter, C. P., Olson, L. y Brené, S. (2005). Moderate ethanol consumption increases hippocampal cell proliferation and neurogenesis in the adult mouse. International Journal of Neuropsychopharmacology, 8: 557-67.
Alves, E., Summavielle, T., Alves, C. J. Gomes-da-Silva, J., Barata, J.C., Fernandes, E., et al. (2007). Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria. Journal of Neuroscience, 27: 10203-10.
Assunção, M., Santos-Marques, M. J., de Freitas, V., Carvalho, F.,
Andrade, J. P., Lukoyanov, N. V. y Paula-Barbosa, M. M. (2007).
Red wine antioxidants protect hippocampal neurons against
ethanol-induced damage: a biochemical, morphological and
behavioral study. Neuroscience, 146: 1581-92.
Bartzokis, G., Beckson, M., Hance, D. B., Lu, P. H., Foster, J. A., Mintz, J.,et al. (1999a). Magnetic resonance imaging evidence of ‘‘silent’’ cerebrovascular toxicity in cocaine dependence. Biological Psychiatry, 45: 1203–11.
Bartzokis, G., Goldstein, I. B, Hance, D. B., Beckson, M., Shapiro, D., Lu, P. H., et al. (1999b). The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients is age-related and region-specific. American Journal of Neuroradiology, 20: 1628–35.
Borges, M. M., Paula-Barbosa, M. M. y Volk, B. (1986). Chronic
alcohol consumption induces lipofuscin deposition in the rat
hippocampus. Neurobiology of Aging, 7: 347-55.
Capela, J. P., Carmo, H., Remião, F., Bastos, M. L., Meisel, A. y Carvalho, F. (2009). Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview. Molecular Neurobiology,39: 10-71 (DOI: 10.1007/s12035-009-8064-1).
Carnes, B. A., Staats, D. O. y Sonntag, W. E. (2008). Does senescence give rise to disease? Mechanisms of Ageing and Development, 129: 693-9.
Chen, C. Y. y Lin, K. M. (2009). Health consequences of illegal drug use. Current Opinion in Psychiatry, 22: 287-92.
Dowling, G. J., Weiss, S. R. y Condon, T. P. (2008). Drugs of abuse and the aging brain. Neuropsychopharmacology, 33: 209-18.
Eisch, A. J. y Harburg, G. C. (2006). Opiates, psychostimulants, and adult hippocampal neurogenesis: Insights for addiction and
stem cell biology. Hippocampus, 16: 271-86.
Hernández-Rabaza, V., Domínguez-Escribà, L., Barcia, J. A., Rosel, J. F., Romero, F. J., García-Verdugo, J. M. y Canales, J. J. (2006). Binge administration of 3,4 methylenedioxymethamphetamine (“ecstasy”) impairs the survival of neural precursors in adult rat dentate gyrus. Neuropharmacology, 51: 967-73.
Herrera, D. G., Yague, A. G., Johnsen-Soriano, S., Bosch-Morell, F., Collado- Morente, L., Muriach, M., Romero, F. J. y Garcia-
Verdugo, J. M. (2006). Selective impairment of hippocampal
neurogenesis by chronic alcoholism: protective effects of an
antioxidant. Proceedings National Academy of Sciences USA,
: 7919-24.
Jaatinen, P., Kiianmaa, K. y Hervonen, A. (1992). Lifelong ethanol consumption enhances the age-related changes in rat
sympathetic neurons. Mechanisms of Ageing and Development,
: 193-5.
Jaatinen, P., Saukko, P. y Hervonen, A. (1993). Chronic ethanol
exposure increases lipopigment accumulation in human heart.
Alcohol and Alcoholism; 28: 559-69.
Kishi, M., Maeyama, S., Koike, J., Aida, Y., Yoshida, H. y Uchikoshi T. (1996). Correlation between intrasinusoidal neutrophilic infiltration and ceroid-lipofuscinosis in alcoholic liver fibrosis with or without fatty change: clinicopathological comparison with nutritional fatty liver. Alcoholism Clinical Experimental Research, 20: 366A-370A.
Lewandowska, E., Kujawa, M., Jedrzejewska, A. (1994). Ethanol-induced changes in Purkinje cells of rat cerebellum. II. The ultrastructural changes after chronic ethanol intoxication. (Morphometric evaluation). Folia Neuropathology, 32: 61-64.
Lombard, D. B., Chua, K. F., Mostoslavsky, R., Franco, S., Gostissa, M. y Alt, F. W. (2005). DNA repair, genome stability, and aging. Cell; 120: 497-512.
Nixon, K., Crews, F. T. (2002). Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. Journal of Neurochemistry; 83: 1087–93.
Paula-Barbosa, M. M., Brandão, F., Madeira, M. D. y Cadete-Leite, A. (1993). Structural changes in the hippocampal formation after long-term alcohol consumption and withdrawal in the rat. Addiction, 88: 237–47.
Poon, H. F., Vaishnav, R. A., Getchell, T. V., Getchell, M. L. y Butterfield, D. A. (2006). Quantitative proteomics analysis of differential protein expression and oxidative modification of specific proteins in the brains of old mice. Neurobiology of Aging, 27: 1010-9.
Rando, T. A. (2006). Stem cells, ageing, and the quest for immortality. Nature, 441: 1080–86.
Rosen, D., Smith, M. L., Reynolds y C. F. (2008). 3rd. The prevalence of mental and physical health disorders among older methadone patients. American Journal of Geriatric Psychiatry, 16: 488-497.
Guardia, J. (2008). ¿Es bueno el alcohol para la salud?Adicciones, 20: 221-35.
Shigenaga, M. K., Hagen, T. M. y Ames, B. N. (1994). Oxidative damage and mitochondrial decay in aging. Proceeding of the National Academy of Sciences of USA, 91: 10771–78.
Schuckit, M. A. (2009). Alcohol-use disorders. Lancet, 373: 492-501.
Terman, A., Brunk, U. T. (2004). Aging as a catabolic malfunction. International Journal of Biochemistry & Cell Biology, 36: 2365-75.
Troen, B. R. (2003). The biology of aging. Mt Sinai Journal of Medicine, 70 : 3-22.
Warner, H. R. (2007). 2006 Kent award lecture: is cell death and
replacement a factor in aging? Journal of Gerontology. A,
Biologycal Sciences and Medical Sciences, 62: 1228-32.
Wu, C. W., Ping, Y. H., Yen, J. C., Chang, C. Y., Wang, S. F., Yeh, C. L., et al. (2007). Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis. Toxicology Applied
Pharmacology, 220: 243-51.
Volkow, N. D., Fowler, J. S., Wang, G. J., Hitzemann, R., Logan, J., Schlyer DJ et al. (1993). Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse, 14: 169–177.
Volkow, N. D., Logan, J., Fowler, J. S., Wang, G. J., Gur, R. C., Wong, C. et al. (2000). Association between age-related decline in brain dopamine activity and impairment in frontal and cingulated metabolism. American Journal of Psychiatry, 157: 75–80.
Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Leonido-Yee, M., Franceschi, D., et al. (2001). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. American Journal of Psychiatry, 158: 377–382.
Vupputuri, S., Batuman, V., Muntner, P., Bazzano, L. A., Lefante, J. J, Whelton, P. K., et al. (2004). The risk for mild kidney function decline associated with illicit drug use among hypertensive men. American Journal of Kidney Disease, 43: 629–635.
Yang, J. L., Weissman, L., Bohr, V. A. y Mattson, M. P. (2008).
Mitochondrial DNA damage and repair in neurodegenerative
disorders. DNA Repair (Amst), 7: 1110-20
