Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms: Table 1.
Open accessAbstract
Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline.
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Limitations of current clinical trials include small recruitment sizes, few measurable clinically-relevant outcomes appropriate for older adults, and need for biomarkers tracking pharmacokinetic, pharmacodynamic, and mechanistic properties and serving as surrogate endpoints.
“Limitations of current clinical trials include small recruitment sizes, the paucity of measurable, clinically-relevant outcomes appropriate for older adults, as well as the need for biomarkers that follow pharmacokinetic, pharmacodynamic, and mechanistic properties of study drugs and could serve as surrogate endpoints [92–94].”
From Reducing Senescent Cell Burden in Aging and Disease (2020) · cites this paper as [92]
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- Authors
- Burd, C. E., Gill, M. S., Niedernhofer, L. J., Robbins, P. D., Austad, S. N., Barzilai, N., & Kirkland, J. L.
- Affiliations
- The Ohio State University (US)
- Scripps Research Institute (US)
- University of Alabama at Birmingham (US)
- Albert Einstein College of Medicine (US)
- Mayo Clinic (US)
- Corresponding author
- Burd, Christin E.
- Gill, Matthew S.
- ORCID
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-16
- Volume
- 71
- Issue
- 11
- Pages
- 1388-1394
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC5055650
- OpenAlex
- W2510623374
- Cited by
- 28
- References
- 46
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 1 · 2017: 6
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- The Journals of Gerontology Series A (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (R24 AG044396)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Reproductive Medicine › Science, Research, and Medicine
- Keywords
- anti-aging therapeutics, preclinical drug development, drug discovery, lead compound development, preclinical biomarkers, research funding, clinician-researcher collaboration, geroscience
- MeSH terms
- Aging, Animals, Clinical Trials as Topic, Congresses as Topic, Disease Models, Animal, Drug Evaluation, Preclinical, Geriatrics, Humans, Biomedical Research
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