Body-wide multi-omic counteraction of aging with GLP-1R agonism

Area of Science:

• Gerontology
• Molecular Biology
• Pharmacology

Background:

• Aging is associated with degenerative disorders, necessitating novel therapeutic strategies.
• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known for various physiological effects.
• Understanding GLP-1RA's impact on aging mechanisms is crucial for developing interventions.

Purpose of the Study:

• To investigate the anti-aging potential of GLP-1RA treatment in aged male mice.
• To explore the molecular and functional changes induced by GLP-1RA in the context of aging.
• To compare GLP-1RA's effects with established anti-aging interventions like mTOR inhibition.

Main Methods:

• Deep molecular profiling and functional assessments were performed on aging male mice.
• Mice received GLP-1RA treatment at different ages (11 months and 18 months) for varying durations.
• Comparative analysis with mammalian target of rapamycin (mTOR) inhibition was conducted.

Main Results:

• GLP-1RA treatment broadly counteracted age-related molecular and functional changes in aged mice.
• The observed anti-aging effects were specific to aged mice and not seen in young adults.
• Treatment initiated later in life showed even stronger molecular age-counteracting effects, dependent on hypothalamic GLP-1R.
• Multi-omic similarities were found between GLP-1RA treatment and mTOR inhibition.

Conclusions:

• GLP-1RA treatment demonstrates significant age-counteracting effects in mice, suggesting therapeutic potential.
• The findings highlight a brain-body axis modulated by GLP-1R in aging.
• GLP-1RAs may offer pleiotropic benefits relevant to anti-aging strategies and clinical development.