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Mitotic Dysfunction Associated with Aging Hallmarks

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Cell Division Machinery and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1002))

Abstract

Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194–1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

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Notes

  1. 1.

    Chromosome content that is not an exact multiple of the haploid complement; imbalanced karyotype.

  2. 2.

    Segregation of a whole chromosome to the incorrect daughter cell during mitosis.

  3. 3.

    Gains or losses of entire chromosomes arising from mis-segregation events during cell division; generally denotes a diploid organism with subpopulations of aneuploid somatic cells.

  4. 4.

    Part of the chromosome comprised of repetitive DNA where the sister-chromatids are connected and the kinetochores assembled.

  5. 5.

    Large protein complex that allows the attachment of chromosomes to spindle microtubules.

  6. 6.

    Surveillance mechanism that halts cell cycle progression until all chromosomes are correctly attached to the spindle.

  7. 7.

    The main microtubule-organizing center of the cell, which contains the centrioles (in animal cells) and duplicates before mitosis to form a bipolar spindle.

  8. 8.

    Chromosome that is left behind at the spindle equator when all the other chromosomes have segregated to opposite spindle poles.

  9. 9.

    Group of rare diseases caused by mutations in genes functionally linked to formation/maintenance of nuclear lamina.

  10. 10.

    A condition in which aging features arise early in life.

  11. 11.

    Features of late-life aging in young individuals, as for instance grey hair, cataracts and body mass loss.

  12. 12.

    Partially mimic an aging phenotype; do not include all signs of aging.

  13. 13.

    Refers to an essentially irreversible growth arrest that occurs when cells that can divide encounter oncogenic stress (for instance, strong mitogenic signals); it is a secondary aging hallmark or compensatory response to primary causes of cellular damage.

  14. 14.

    Stretched chromatin structure in between two daughter cells.

  15. 15.

    Small nucleus in a daughter cell generated by chromosome mis-segregation.

  16. 16.

    Vesicular membraneous matrix that embeds the microtubule spindle apparatus during mitosis.

  17. 17.

    Natural or chronological aging.

  18. 18.

    Increased frequency of chromosome mis-segregation events.

  19. 19.

    Microtubule bundles that attach sister kinetochores to spindle poles and power chromosome movement during mitosis.

  20. 20.

    Multiprotein complex with ubiquitin-ligase activity that is responsible for the ubiquitination of numerous key cell-cycle regulators.

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    Authors and Affiliations

    1. Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde – i3S, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal

      Joana Catarina Macedo, Sara Vaz & Elsa Logarinho

    2. Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

      Elsa Logarinho

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    1. Joana Catarina Macedo
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    2. Sara Vaz
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    3. Elsa Logarinho
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    Correspondence to Elsa Logarinho .

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    1. Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva University, Geneva, Switzerland

      Monica Gotta

    2. Department of Cell Physiology and Metabolism, Faculty of Medicine, Geneva University, Geneva, Switzerland

      Patrick Meraldi

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    Macedo, J.C., Vaz, S., Logarinho, E. (2017). Mitotic Dysfunction Associated with Aging Hallmarks. In: Gotta, M., Meraldi, P. (eds) Cell Division Machinery and Disease. Advances in Experimental Medicine and Biology, vol 1002. Springer, Cham. https://doi.org/10.1007/978-3-319-57127-0_7

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