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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

Author

Listed:
  • David E. Harrison

    (The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Randy Strong

    (Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, Texas 78229, USA)

  • Zelton Dave Sharp

    (and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, Texas 78245, USA)

  • James F. Nelson

    (Texas 78229, USA)

  • Clinton M. Astle

    (The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Kevin Flurkey

    (The Jackson Laboratory, Bar Harbor, Maine 04609, USA)

  • Nancy L. Nadon

    (National Institute on Aging, Bethesda, Maryland 20892, USA)

  • J. Erby Wilkinson

    (Unit for Laboratory Animal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-2200, USA)

  • Krystyna Frenkel

    (Environmental Medicine, NY University School of Medicine)

  • Christy S. Carter

    (Wake Forest University School of Medicine, North Carolina 27157, USA
    Present address: Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, Florida 32611, USA.)

  • Marco Pahor

    (Wake Forest University School of Medicine, North Carolina 27157, USA
    Present address: Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, Florida 32611, USA.)

  • Martin A. Javors

    (The University of Texas Health Science Center at San Antonio, Texas 78229, USA)

  • Elizabeth Fernandez

    (Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, Texas 78229, USA)

  • Richard A. Miller

    (University of Michigan, and Ann Arbor VA Medical Center, Ann Arbor, Michigan 48109-2200, USA)

Abstract

Rapamycin for a longer life? The antitumour drug rapamycin targets TOR, a kinase that is part of the PI3K–AKT–mTOR cascade, involved in regulating protein translation, cell growth and autophagy. Reducing TOR function is known to extend the life of yeast, worms and flies. Now experiments replicated in three different laboratories demonstrate that rapamycin, fed to male and female mice in a dose that substantially inhibits TOR signalling, can extend their median and maximal lifespan by up to 14%. This life extension was observed in mice fed rapamycin from 270 days of age and also at a late stage in their life, from age 600 days. These findings point to the TOR pathway as a critical point in the control of ageing in mammals and in the pathogenesis of late-life illnesses.

Suggested Citation

  • David E. Harrison & Randy Strong & Zelton Dave Sharp & James F. Nelson & Clinton M. Astle & Kevin Flurkey & Nancy L. Nadon & J. Erby Wilkinson & Krystyna Frenkel & Christy S. Carter & Marco Pahor & Ma, 2009. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice," Nature, Nature, vol. 460(7253), pages 392-395, July.
    • Handle: RePEc:nat:nature:v:460:y:2009:i:7253:d:10.1038_nature08221
    DOI: 10.1038/nature08221
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    Cited by:

    1. Debonneuil, Edouard & Loisel, Stéphane & Planchet, Frédéric, 2018. "Do actuaries believe in longevity deceleration?," Insurance: Mathematics and Economics, Elsevier, vol. 78(C), pages 325-338.
    2. Kan Xie & Helmut Fuchs & Enzo Scifo & Dan Liu & Ahmad Aziz & Juan Antonio Aguilar-Pimentel & Oana Veronica Amarie & Lore Becker & Patricia da Silva-Buttkus & Julia Calzada-Wack & Yi-Li Cho & Yushuang , 2022. "Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice," Nature Communications, Nature, vol. 13(1), pages 1-29, December.
    3. Jae Sung Lim & Eun Jae Jeon & Hye Sun Go & Hyung-Jin Kim & Kye Young Kim & Thi Quynh Trang Nguyen & Da Young Lee & Kyu Suk Kim & Federico Pietrocola & Seol Hee Hong & Shee Eun Lee & Kyoung-Shim Kim & , 2024. "Mucosal TLR5 activation controls healthspan and longevity," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Daniel J. Ham & Anastasiya Börsch & Kathrin Chojnowska & Shuo Lin & Aurel B. Leuchtmann & Alexander S. Ham & Marco Thürkauf & Julien Delezie & Regula Furrer & Dominik Burri & Michael Sinnreich & Chris, 2022. "Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Juan Ignacio Jiménez-Loygorri & Beatriz Villarejo-Zori & Álvaro Viedma-Poyatos & Juan Zapata-Muñoz & Rocío Benítez-Fernández & María Dolores Frutos-Lisón & Francisco A. Tomás-Barberán & Juan Carlos Es, 2024. "Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Marcin Pilarczyk & Mehdi Fazel-Najafabadi & Michal Kouril & Behrouz Shamsaei & Juozas Vasiliauskas & Wen Niu & Naim Mahi & Lixia Zhang & Nicholas A. Clark & Yan Ren & Shana White & Rashid Karim & Huan, 2022. "Connecting omics signatures and revealing biological mechanisms with iLINCS," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Cox, Lynne S., 2022. "Therapeutic approaches to treat and prevent age-related diseases through understanding the underlying biological drivers of ageing," The Journal of the Economics of Ageing, Elsevier, vol. 23(C).
    8. Betz, Ulrich A.K. & Arora, Loukik & Assal, Reem A. & Azevedo, Hatylas & Baldwin, Jeremy & Becker, Michael S. & Bostock, Stefan & Cheng, Vinton & Egle, Tobias & Ferrari, Nicola & Schneider-Futschik, El, 2023. "Game changers in science and technology - now and beyond," Technological Forecasting and Social Change, Elsevier, vol. 193(C).
    9. Reji Babygirija & Michelle M. Sonsalla & Jericha Mill & Isabella James & Jessica H. Han & Cara L. Green & Mariah F. Calubag & Gina Wade & Anna Tobon & John Michael & Michaela M. Trautman & Ryan Matosk, 2024. "Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    10. Konstantin Avchaciov & Marina P. Antoch & Ekaterina L. Andrianova & Andrei E. Tarkhov & Leonid I. Menshikov & Olga Burmistrova & Andrei V. Gudkov & Peter O. Fedichev, 2022. "Unsupervised learning of aging principles from longitudinal data," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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