Articles producció científica> Medicina i Cirurgia

In silico clinical trials for anti-aging therapies

  • Identification data

    Identifier: imarina:5825619
    Authors:
    Menendez JCuyàs EFolguera-Blasco NVerdura SMartin-Castillo BJoven JAlarcón T
    Abstract:
    Therapeutic strategies targeting the hallmarks of aging can be broadly grouped into four categories, namely systemic (blood) factors, metabolic manipulation (diet regimens and dietary restriction mimetics), suppression of cellular senescence (senolytics), and cellular reprogramming, which likely have common characteristics and mechanisms of action. In evaluating the potential synergism of combining such strategies, however, we should consider the possibility of constraining trade-off phenotypes such as impairment in wound healing and immune response, tissue dysfunction and tumorigenesis. Moreover, we are rapidly learning that the benefit/risk ratio of aging-targeted interventions largely depends on intra- and inter-individual variations of susceptibility to the healthspan-, resilience-, and/or lifespan-promoting effects of the interventions. Here, we exemplify how computationally-generated proxies of the efficacy of a given lifespan/healthspan-promoting approach can predict the impact of baseline epigenetic heterogeneity on the positive outcomes of ketogenic diet and mTOR inhibition as single or combined anti-aging strategies. We therefore propose that stochastic biomathematical modeling and computational simulation platforms should be developed as in silico strategies to accelerate the performance of clinical trials targeting human aging, and to provide personalized approaches and robust biomarkers of healthy aging at the individual-to-population levels.
  • Others:

    Author, as appears in the article.: Menendez J; Cuyàs E; Folguera-Blasco N; Verdura S; Martin-Castillo B; Joven J; Alarcón T
    Department: Medicina i Cirurgia
    URV's Author/s: Joven Maried, Jorge
    Keywords: Senolytics Inflammation Cancer Biomathematics Aging
    Abstract: Therapeutic strategies targeting the hallmarks of aging can be broadly grouped into four categories, namely systemic (blood) factors, metabolic manipulation (diet regimens and dietary restriction mimetics), suppression of cellular senescence (senolytics), and cellular reprogramming, which likely have common characteristics and mechanisms of action. In evaluating the potential synergism of combining such strategies, however, we should consider the possibility of constraining trade-off phenotypes such as impairment in wound healing and immune response, tissue dysfunction and tumorigenesis. Moreover, we are rapidly learning that the benefit/risk ratio of aging-targeted interventions largely depends on intra- and inter-individual variations of susceptibility to the healthspan-, resilience-, and/or lifespan-promoting effects of the interventions. Here, we exemplify how computationally-generated proxies of the efficacy of a given lifespan/healthspan-promoting approach can predict the impact of baseline epigenetic heterogeneity on the positive outcomes of ketogenic diet and mTOR inhibition as single or combined anti-aging strategies. We therefore propose that stochastic biomathematical modeling and computational simulation platforms should be developed as in silico strategies to accelerate the performance of clinical trials targeting human aging, and to provide personalized approaches and robust biomarkers of healthy aging at the individual-to-population levels.
    Thematic Areas: Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Geriatrics & gerontology Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología
    ISSN: 19454589
    Author's mail: jorge.joven@urv.cat
    Author identifier: 0000-0003-2749-4541
    Record's date: 2024-09-07
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Aging-Us. 11 (16): 6591-6601
    APA: Menendez J; Cuyàs E; Folguera-Blasco N; Verdura S; Martin-Castillo B; Joven J; Alarcón T (2019). In silico clinical trials for anti-aging therapies. Aging-Us, 11(16), 6591-6601. DOI: 10.18632/aging.102180
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2019
    Publication Type: Journal Publications
  • Keywords:

    Cell Biology,Geriatrics & Gerontology
    Senolytics
    Inflammation
    Cancer
    Biomathematics
    Aging
    Odontología
    Nutrição
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Geriatrics & gerontology
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Biotecnología
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