hNAG-1 increases lifespan by regulating energy metabolism and insulin/IGF-1/mTOR signaling
Open accessAbstract
Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) or GDF15 is a divergent member of the transforming growth factor beta (TGF-β) superfamily and mice expressing hNAG-1/hGDF15 have been shown to be resistant to HFD-induced obesity and inflammation. This study investigated if hNAG-1 increases lifespan in mice and its potential mechanisms. Here we report that female hNAG-1 mice had significantly increased both mean and median life spans in two transgenic lines, with a larger difference in life spans in mice on a HFD than on low fat diet. hNAG-1 mice displayed significantly reduced body and adipose tissue weight, lowered serum IGF-1, insulin and glucose levels, improved insulin sensitivity, and increased oxygen utilization, oxidative metabolism and energy expenditure. Gene expression analysis revealed significant differences in conserved gene pathways that are important regulators of longevity, including IGF-1, p70S6K, and PI3K/Akt signaling cascades. Phosphorylation of major components of IGF-1/mTOR signaling pathway was significantly lower in hNAG-1mice. Collectively, hNAG-1 is an important regulator of mammalian longevity and may act as a survival factor. Our study suggests that hNAG-1 has potential therapeutic uses in obesity-related diseases where life span is frequently shorter.
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Mice overexpressing human GDF15 display increased lifespan.
“mice overexpressing human GDF15 display increased life span (23).”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [23]
Mice overexpressing human GDF15 display increased life span.
“Moreover, mice overexpressing human GDF15 display increased life span (23).”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [23]
GDF15 transgenic mice exhibit longer lifespan when fed normal chow and high-fat diets.
“GDF15 transgenic mice also exhibited a longer lifespan when fed both normal chow and high-fat diets, suggesting its role as a survival factor [209].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [209]
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- Authors
- Wang, X., Chrysovergis, K., Kosak, J., Kissling, G., Streicker, M., Moser, G., Li, R., & Eling, T. E.
- Affiliations
- Zhejiang Chinese Medical University (CN)
- National Institute of Environmental Health Sciences (US)
- Integrated Laboratory Systems, Inc. (US)
- Corresponding author
- Eling, Thomas E.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2014-08-28
- Volume
- 6
- Issue
- 8
- Pages
- 690-704
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC4169862
- OpenAlex
- W2166617870
- Cited by
- 106
- References
- 36
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 14 · 2020: 19 · 2019: 10 · 2018: 10 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (Z01ES010016, Z01-ES010016-14)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- GDF15, lifespan extension, longevity, energy metabolism, high-fat diet, obesity, insulin sensitivity, oxidative metabolism, energy expenditure, PI3K/Akt signaling, p70S6K, adipose tissue, transgenic mice
- MeSH terms
- Animals, Body Weight, Energy Metabolism, Female, Insulin, Insulin Resistance, Insulin-Like Growth Factor I, Longevity, Phosphorylation, Signal Transduction, Mice, Growth Differentiation Factor 15, TOR Serine-Threonine Kinases
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