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The Genetics of Exceptional Longevity in Humans and Relevance to Healthy Aging

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Current Perspectives on Centenarians

Part of the book series: International Perspectives on Aging ((Int. Perspect. Aging,volume 36))

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Abstract

Exceptional longevity aggregates in families, consistent with a genetic contribution to living a very long life. Understanding the genetic underpinnings of exceptional longevity may point to therapeutic targets for healthy aging and lifespan extension. This chapter first provides a review of the evidence for familial aggregation of exceptional lifespan and then summarizes biological insights about aging trajectories gleaned from rare syndromes associated with accelerated aging (progeroid syndromes) and animal models for which single gene mutations have been associated with marked extension of lifespan. We then describe how some of the signaling pathways first identified in animal models of lifespan extension may relate to caloric restriction, which constitutes one of the most robust interventions available to extend lifespan in humans. Finally, we describe the some of the challenges in current efforts to identify lifespan-extending genetic variants in humans.

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Author information

Authors and Affiliations

  1. Departments of Medicine and Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA

    Braxton D. Mitchell

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  1. Braxton D. Mitchell
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Correspondence to Braxton D. Mitchell .

Editor information

Editors and Affiliations

  1. University of Maryland School of Medicine, Baltimore, MD, USA

    Raya Elfadel Kheirbek

  2. Department of Veterans Affairs, Washington, DC, USA

    Maria D. Llorente

Multiple Choice Questions

Multiple Choice Questions

  1. 1.

    The most robust lifespan enhancing intervention is:

    1. A.

      Exercise

    2. B.

      Meditation

    3. C.

      Caloric restriction

    4. D.

      Vegetarian diet

      CORRECT RESPONSE: C

  2. 2.

    The insights most relevant to exceptional lifespan in humans that have been provided by animal models of extreme longevity pertain to:

    1. A.

      DNA repair

    2. B.

      Nutrition sensors and signaling pathways

    3. C.

      Disease resistance

      CORRECT RESPONSE: B

  3. 3.

    Human progerion syndromes are mostly due to:

    1. A.

      Mutations in genes related to DNA repair and cell instability

    2. B.

      Mutations in genes related to signaling pathways related to nutrition sensing

    3. C.

      Chromosome abnormalities

    4. D.

      Autosomal dominant disorders

      CORRECT RESPONSE: A

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Mitchell, B.D. (2023). The Genetics of Exceptional Longevity in Humans and Relevance to Healthy Aging. In: Kheirbek, R.E., Llorente, M.D. (eds) Current Perspectives on Centenarians. International Perspectives on Aging, vol 36. Springer, Cham. https://doi.org/10.1007/978-3-031-30915-1_3

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  • DOI: https://doi.org/10.1007/978-3-031-30915-1_3

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-031-30915-1

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