IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34051-9.html
   My bibliography  Save this article

Unsupervised learning of aging principles from longitudinal data

Author

Listed:
  • Konstantin Avchaciov

    (Gero PTE. LTD.)

  • Marina P. Antoch

    (Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center)

  • Ekaterina L. Andrianova

    (Genome Protection, Inc.)

  • Andrei E. Tarkhov

    (Gero PTE. LTD.)

  • Leonid I. Menshikov

    (Gero PTE. LTD.)

  • Olga Burmistrova

    (Gero PTE. LTD.)

  • Andrei V. Gudkov

    (Genome Protection, Inc.
    Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center)

  • Peter O. Fedichev

    (Gero PTE. LTD.)

Abstract

Age is the leading risk factor for prevalent diseases and death. However, the relation between age-related physiological changes and lifespan is poorly understood. We combined analytical and machine learning tools to describe the aging process in large sets of longitudinal measurements. Assuming that aging results from a dynamic instability of the organism state, we designed a deep artificial neural network, including auto-encoder and auto-regression (AR) components. The AR model tied the dynamics of physiological state with the stochastic evolution of a single variable, the “dynamic frailty indicator” (dFI). In a subset of blood tests from the Mouse Phenome Database, dFI increased exponentially and predicted the remaining lifespan. The observation of the limiting dFI was consistent with the late-life mortality deceleration. dFI changed along with hallmarks of aging, including frailty index, molecular markers of inflammation, senescent cell accumulation, and responded to life-shortening (high-fat diet) and life-extending (rapamycin) treatments.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34051-9
    DOI: 10.1038/s41467-022-34051-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34051-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-34051-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jan M. van Deursen, 2014. "The role of senescent cells in ageing," Nature, Nature, vol. 509(7501), pages 439-446, May.
    2. Johnstone, Iain M. & Lu, Arthur Yu, 2009. "On Consistency and Sparsity for Principal Components Analysis in High Dimensions," Journal of the American Statistical Association, American Statistical Association, vol. 104(486), pages 682-693.
    3. Marco Baggiolini, 1998. "Chemokines and leukocyte traffic," Nature, Nature, vol. 392(6676), pages 565-568, April.
    4. Andreas Mardt & Luca Pasquali & Hao Wu & Frank Noé, 2018. "VAMPnets for deep learning of molecular kinetics," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    5. Michael B. Schultz & Alice E. Kane & Sarah J. Mitchell & Michael R. MacArthur & Elisa Warner & David S. Vogel & James R. Mitchell & Susan E. Howlett & Michael S. Bonkowski & David A. Sinclair, 2020. "Publisher Correction: Age and life expectancy clocks based on machine learning analysis of mouse frailty," Nature Communications, Nature, vol. 11(1), pages 1-1, December.
    6. Bethany Lusch & J. Nathan Kutz & Steven L. Brunton, 2018. "Deep learning for universal linear embeddings of nonlinear dynamics," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    7. 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.
    8. Andreas Mardt & Luca Pasquali & Hao Wu & Frank Noé, 2018. "Author Correction: VAMPnets for deep learning of molecular kinetics," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    9. Michael B. Schultz & Alice E. Kane & Sarah J. Mitchell & Michael R. MacArthur & Elisa Warner & David S. Vogel & James R. Mitchell & Susan E. Howlett & Michael S. Bonkowski & David A. Sinclair, 2020. "Age and life expectancy clocks based on machine learning analysis of mouse frailty," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    10. Marten Scheffer & Jordi Bascompte & William A. Brock & Victor Brovkin & Stephen R. Carpenter & Vasilis Dakos & Hermann Held & Egbert H. van Nes & Max Rietkerk & George Sugihara, 2009. "Early-warning signals for critical transitions," Nature, Nature, vol. 461(7260), pages 53-59, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Carolin Thomas & Reto Erni & Jia Yee Wu & Fabian Fischer & Greta Lamers & Giovanna Grigolon & Sarah J. Mitchell & Kim Zarse & Erick M. Carreira & Michael Ristow, 2023. "A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Corneel Casert & Isaac Tamblyn & Stephen Whitelam, 2024. "Learning stochastic dynamics and predicting emergent behavior using transformers," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    3. Benjamin D Lee & Anthony Gitter & Casey S Greene & Sebastian Raschka & Finlay Maguire & Alexander J Titus & Michael D Kessler & Alexandra J Lee & Marc G Chevrette & Paul Allen Stewart & Thiago Britto-, 2022. "Ten quick tips for deep learning in biology," PLOS Computational Biology, Public Library of Science, vol. 18(3), pages 1-20, March.
    4. Giacomo Janson & Gilberto Valdes-Garcia & Lim Heo & Michael Feig, 2023. "Direct generation of protein conformational ensembles via machine learning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Cristal M. Hill & Diana C. Albarado & Lucia G. Coco & Redin A. Spann & Md Shahjalal Khan & Emily Qualls-Creekmore & David H. Burk & Susan J. Burke & J. Jason Collier & Sangho Yu & David H. McDougal & , 2022. "FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Joshua S. North & Christopher K. Wikle & Erin M. Schliep, 2023. "A Review of Data‐Driven Discovery for Dynamic Systems," International Statistical Review, International Statistical Institute, vol. 91(3), pages 464-492, December.
    7. Richter, Andries & Dakos, Vasilis, 2015. "Profit fluctuations signal eroding resilience of natural resources," Ecological Economics, Elsevier, vol. 117(C), pages 12-21.
    8. Puyi Fang & Zhaoxing Gao & Ruey S. Tsay, 2023. "Determination of the effective cointegration rank in high-dimensional time-series predictive regressions," Papers 2304.12134, arXiv.org, revised Apr 2023.
    9. Candelon, B. & Hurlin, C. & Tokpavi, S., 2012. "Sampling error and double shrinkage estimation of minimum variance portfolios," Journal of Empirical Finance, Elsevier, vol. 19(4), pages 511-527.
    10. Fan, Jianqing & Jiang, Bai & Sun, Qiang, 2022. "Bayesian factor-adjusted sparse regression," Journal of Econometrics, Elsevier, vol. 230(1), pages 3-19.
    11. Karimi Rahjerdi, Bahareh & Ramamoorthy, Ramesh & Nazarimehr, Fahimeh & Rajagopal, Karthikeyan & Jafari, Sajad, 2022. "Indicating the synchronization bifurcation points using the early warning signals in two case studies: Continuous and explosive synchronization," Chaos, Solitons & Fractals, Elsevier, vol. 164(C).
    12. Yata, Kazuyoshi & Aoshima, Makoto, 2013. "PCA consistency for the power spiked model in high-dimensional settings," Journal of Multivariate Analysis, Elsevier, vol. 122(C), pages 334-354.
    13. Asai, Manabu & McAleer, Michael, 2015. "Forecasting co-volatilities via factor models with asymmetry and long memory in realized covariance," Journal of Econometrics, Elsevier, vol. 189(2), pages 251-262.
    14. John M Drake & Tobias S Brett & Shiyang Chen & Bogdan I Epureanu & Matthew J Ferrari & Éric Marty & Paige B Miller & Eamon B O’Dea & Suzanne M O’Regan & Andrew W Park & Pejman Rohani, 2019. "The statistics of epidemic transitions," PLOS Computational Biology, Public Library of Science, vol. 15(5), pages 1-14, May.
    15. James J Elser & Timothy J Elser & Stephen R Carpenter & William A Brock, 2014. "Regime Shift in Fertilizer Commodities Indicates More Turbulence Ahead for Food Security," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-7, May.
    16. Roland Clift & Sarah Sim & Henry King & Jonathan L. Chenoweth & Ian Christie & Julie Clavreul & Carina Mueller & Leo Posthuma & Anne-Marie Boulay & Rebecca Chaplin-Kramer & Julia Chatterton & Fabrice , 2017. "The Challenges of Applying Planetary Boundaries as a Basis for Strategic Decision-Making in Companies with Global Supply Chains," Sustainability, MDPI, vol. 9(2), pages 1-23, February.
    17. 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.
    18. Darrell Jiajie Tay & Chung-I Chou & Sai-Ping Li & Shang You Tee & Siew Ann Cheong, 2016. "Bubbles Are Departures from Equilibrium Housing Markets: Evidence from Singapore and Taiwan," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-13, November.
    19. Maillet, Bertrand & Tokpavi, Sessi & Vaucher, Benoit, 2015. "Global minimum variance portfolio optimisation under some model risk: A robust regression-based approach," European Journal of Operational Research, Elsevier, vol. 244(1), pages 289-299.
    20. Fushing, Hsieh & Jordà, Òscar & Beisner, Brianne & McCowan, Brenda, 2014. "Computing systemic risk using multiple behavioral and keystone networks: The emergence of a crisis in primate societies and banks," International Journal of Forecasting, Elsevier, vol. 30(3), pages 797-806.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34051-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.