SS-31 and NMN: Two paths to improve metabolism and function in aged hearts

Area of Science:

• Cardiology
• Mitochondrial Biology
• Gerontology

Background:

• Aging leads to cardiac dysfunction and reduced mitochondrial health.
• Mitochondrial-targeted therapies, such as SS-31 and nicotinamide mononucleotide (NMN), show promise in combating age-related decline.

Purpose of the Study:

• To investigate the individual and combined effects of SS-31 and NMN on age-related heart dysfunction in mice.
• To assess the impact of these treatments on cardiac function, cellular metabolism, and mitochondrial energetics.

Main Methods:

• Echocardiography was used to evaluate cardiac function (systolic and diastolic).
• Metabolomic analysis and magnetic resonance spectroscopy (MRS) assessed cellular energy status and NAD+/NADH dynamics.
• Mice were treated with SS-31, NMN, or a combination, and compared to young and old controls.

Main Results:

• SS-31 partially improved diastolic function, while NMN fully restored systolic function in aged hearts.
• Both treatments increased NAD+ turnover; combined treatment significantly elevated steady-state NAD(H) levels.
• Both drugs normalized the age-related decline in phosphocreatine/ATP ratio under workload, indicating restored energetic capacity.

Conclusions:

• SS-31 and NMN individually restore distinct aspects of mitochondrial and cardiac health in aging hearts.
• Combined SS-31 and NMN treatment exhibits synergistic effects, rejuvenating aged hearts and recapitulating a younger physiological state.
• These findings highlight the therapeutic potential of combining mitochondrial-targeting agents for age-related cardiovascular diseases.