Mitotic Dysfunction Associated with Aging Hallmarks.
Joana Catarina Macedo1, Sara Vaz1, Elsa Logarinho2,3
1Aging 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.
Advances in Experimental Medicine and Biology
|June 11, 2017
Summary
Aging is linked to aneuploidy (aberrant chromosome numbers). This review explores how aging hallmarks contribute to aneuploidy and how aneuploidy impacts aging, suggesting improved mitotic fidelity could extend lifespan.
Area of Science:
- Gerontology and Molecular Biology
- Cellular Biology and Genetics
Background:
- Aging is a biological process involving progressive functional decline and increased risk for chronic diseases.
- Aneuploidy, an abnormal chromosome number, is increasingly linked to aging, but underlying mechanisms are unclear.
- Key aging hallmarks include genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis.
Purpose of the Study:
- To review the connection between aging hallmarks and the loss of chromosome segregation fidelity.
- To explore the systemic impacts of aneuploidy on cell physiology and its relation to aging hallmarks.
- To propose a bidirectional relationship between aging and aneuploidy.
Main Methods:
- Literature review of studies investigating aging hallmarks and chromosome segregation.
- Analysis of research on the cellular and systemic effects of aneuploidy.
- Synthesis of evidence to support a mutual causality model.
Main Results:
- Aging hallmarks can compromise chromosome segregation fidelity, leading to aneuploidy.
- Aneuploidy contributes to cellular dysfunction and exhibits characteristics of aging hallmarks.
- A complex interplay exists between the aging process and the development of aneuploidy.
Conclusions:
- A mutual causality is proposed between aging and aneuploidy.
- Modulating mitotic fidelity presents a potential therapeutic strategy to promote healthy aging.
- Further research is needed to elucidate the precise molecular links and therapeutic targets.
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