At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways
Open accessAbstract
The metabolic syndrome is becoming increasingly prevalent in the general population and carries significant incremental morbidity and mortality. It is associated with multi-organ involvement and increased all-cause mortality, resembling a precocious aging process. The mechanisms that account for this phenomenon are incompletely known, but it is becoming clear that longevity genes might be involved. Experiments with overactivation or disruption of key lifespan determinant pathways, such as silent information regulator (SIR)T1, p66Shc, and mammalian target of rapamycin (TOR), lead to development of features of the metabolic syndrome in mice. These genes integrate longevity pathways and metabolic signals in a complex interplay in which lifespan appears to be strictly dependent on substrate and energy bioavailability. Herein, we describe the roles and possible interconnections of selected lifespan determinant molecular networks in the development of the metabolic syndrome and its complications, describing initial available data in humans. Additional pathways are involved in linking nutrient availability and longevity, certainly including insulin and Insulin-like Growth Factor-1 (IGF-1) signaling, as well as FOXO transcription factors. The model described in this viewpoint article is therefore likely to be an oversimplification. Nevertheless, it represents one starting platform for understanding cell biology of lifespan in relation to the metabolic syndrome.
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Metformin is one of the first-line treatments of patients with T2DM, and has also been used to treat patients at risk for T2DM, such as those with metabolic syndrome.
“Metformin is one of the first-line treatments of patients with T2DM, but it has also been used to treat patients at risk for T2DM, such as those with metabolic syndrome (87).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [87]
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Thyroid Hormone Signaling and Homeostasis During Aging
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Adult Stem Cells and Diseases of Aging
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“The interaction of aging and metabolic pathways, including p66SHC, SIRT1, or AMPK/mTOR/S6K (Fadini et al., 2011), with telomere erosion in the presence of diabetes or obesity is a promising field to reveal how metabolic disorders impact on aging.”
Background
- Authors
- Fadini, G. P., Ceolotto, G., Pagnin, E., de Kreutzenberg, S., & Avogaro, A.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Fadini, Gian Paolo
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-11-10
- Volume
- 10
- Issue
- 1
- Pages
- 10-17
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1793096995
- Cited by
- 97
- References
- 86
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 17 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 12
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- metabolic syndrome, longevity, lifespan determination, SIRT1, p66Shc, TOR signaling, insulin signaling, IGF-1 signaling, FOXO transcription factors, aging, energy metabolism, nutrient availability, all-cause mortality
- MeSH terms
- Animals, Drosophila, Female, Humans, Insulin, Longevity, Male, Mice, Transgenic, Nutritive Value, Transcription Factors, Signal Transduction, Caenorhabditis elegans, Receptor Cross-Talk, Metabolic Syndrome, Caloric Restriction, Intracellular Signaling Peptides and Proteins, Mice
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