Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience
Open accessAbstract
Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species.
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Aging increases glucose intolerance, insulin resistance, and diabetes, decreases physical activity and exercise capacity, and impairs skeletal muscle architecture and cardiac function.
“aging leads to an increased incidence of glucose intolerance, insulin resistance, and diabetes, as well as a decrease in physical activity and exercise capacity, and impairment in skeletal muscle architecture and cardiac function”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Huffman et al., 2016
The AMPK pathway is pro-longevity, while the mTOR-p70S6K and ERK pathways negatively correlate with health span.
“We further explored the effect of 78c on pro-longevity pathways, such as the AMPK pathway, and in pathways that negatively correlate with health span, such as the mTOR-p70S6K and ERK pathways (Huffman et al., 2016; Justice et al., 2016).”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Huffman et al., 2016
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Cellular senescence: a translational perspective
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Self-citation
- Authors
- Huffman, D. M., Justice, J. N., Stout, M. B., Kirkland, J. L., Barzilai, N., & Austad, S. N.
- Affiliations
- Albert Einstein College of Medicine (US)
- University of Colorado Boulder (US)
- Mayo Clinic (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Austad, Steven N.
- 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
- 1395-1406
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC5055649
- OpenAlex
- W2507186267
- Cited by
- 52
- References
- 110
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 2 · 2020: 8 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 1
- FWCI
- 3.41
- 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
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- healthspan, mouse models of aging, geroscience, health metrics, stress response, resilience, frailty, multimorbidity
- MeSH terms
- Aged, Aging, Animals, Chronic Disease, Congresses as Topic, Disease Models, Animal, Female, Humans, Longevity, Male, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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