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Proteomic changes induced by longevity-promoting interventions in mice
Adam R Burns1, Jack Wiedrick2, Alicia Feryn2
1Biostatistics & Design Program, Oregon Health & Science University, Portland, OR, USA. burnsad@ohsu.edu.
Abstract:
Using mouse models and high-throughput proteomics, we conducted an in-depth analysis of the proteome changes induced in response to seven interventions known to increase mouse lifespan. This included two genetic mutations, a growth hormone receptor knockout (GHRKO mice) and a mutation in the Pit-1 locus (Snell dwarf mice), four drug treatments (rapamycin, acarbose, canagliflozin, and 17α-estradiol), and caloric restriction. Each of the interventions studied induced variable changes in the concentrations of proteins across liver, kidney, and gastrocnemius muscle tissue samples, with the strongest responses in the liver and limited concordance in protein responses across tissues. To the extent that these interventions promote longevity through common biological mechanisms, we anticipated that proteins associated with longevity could be identified by characterizing shared responses across all or multiple interventions. Many of the proteome alterations induced by each intervention were distinct, potentially implicating a variety of biological pathways as being related to lifespan extension. While we found no protein that was affected similarly by every intervention, we identified a set of proteins that responded to multiple interventions. These proteins were functionally diverse but tended to be involved in peroxisomal oxidation and metabolism of fatty acids. These results provide candidate proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.
Insights
Researchers analyzed proteome changes in mice undergoing lifespan-extending interventions. Key findings point to proteins involved in peroxisomal oxidation and fatty acid metabolism as potential targets for promoting healthy aging.
Area of Science:
- Biochemistry
- Gerontology
- Proteomics
Background:
- Aging is a complex process influenced by various genetic and environmental factors.
- Interventions like caloric restriction and specific drug treatments are known to extend lifespan in model organisms.
- Understanding the molecular mechanisms underlying lifespan extension is crucial for developing strategies to promote healthy aging.
Purpose of the Study:
- To investigate proteome alterations in response to multiple lifespan-extending interventions in mice.
- To identify shared protein changes across different interventions that may indicate common longevity pathways.
- To uncover novel protein candidates and biological mechanisms associated with enhanced longevity.
Main Methods:
- Utilized mouse models subjected to seven distinct lifespan-extending interventions.
- Employed high-throughput proteomics to analyze protein concentration changes in liver, kidney, and muscle tissues.
- Compared proteomic profiles across interventions to identify common and distinct molecular responses.
Main Results:
- Each intervention induced variable proteome changes, with the liver showing the strongest responses.
- Limited concordance in protein responses was observed across different tissue types.
- No single protein was affected by all interventions, but a set of proteins involved in peroxisomal oxidation and fatty acid metabolism responded to multiple interventions.
Conclusions:
- Lifespan-extending interventions trigger diverse proteomic alterations, suggesting multiple pathways contribute to longevity.
- Proteins involved in peroxisomal oxidation and fatty acid metabolism represent promising targets for interventions aimed at promoting healthy aging.
- These findings provide a foundation for future research into therapeutic strategies for age-related diseases and lifespan extension.
