Effects of NMN on the Heart

Cardiovascular disease is the leading cause of death in the elderly. In addition, age-related declines in cardiac function, including diastolic and systolic dysfunction, have been shown to be strongly associated with frailty. As cardiac dysfunction places a tremendous burden on older adults, the development of treatments that can improve heart health in older adults remains a top priority for extending the healthy human lifespan.

Most of the volume of the heart consists of cardiomyocytes, which must meet the incredible energy demands of continuous contraction and diastole throughout their life cycle. To meet this energy demand, cardiac tissue has one of the highest mitochondrial densities in the body. As cells age, nicotinamide dinucleotide (NAD+ ) levels, ATP output, and mitochondrial biogenesis decrease, while oxidative stress, mtDNA damage, and mitochondrial structural changes increase. Based on these physiological characteristics, it has long been hypothesized that mitochondrial health is critical for maintaining cardiac health. Based on this hypothesis, therapies capable of restoring the mitochondrial parameters of aging cardiomyocytes to a more youthful state have the potential to repair the function of the aging heart.

The researchers studied the effects of NMN on cardiac function and metabolism in aged mice.

NMN is a naturally occurring nucleotide precursor of NAD+ that is produced via the NAD+ remediation pathway. NMN improves mitochondrial health by increasing cellular NAD+ availability, which in turn improves energy capacity and activates silencer-regulated protein deacetylase activity. Recent studies have provided strong evidence for this hypothesis and have shown that NMN supplementation enhances NAD+ availability and improves many of the classic signs of aging in mice. NMN supplementation has also been shown to partially restore cardiac function in a mouse model of heart failure.

Studies have demonstrated that NMN significantly improves diastolic and high-load systolic function and may be effective in reducing age-related cardiac hypertrophy.

Reference:

Whitson JA, Bitto A, Zhang H, Sweetwyne MT, Coig R, Bhayana S, Shankland EG, Wang L, Bammler TK, Mills KF, Imai SI, Conley KE, Marcinek DJ, Rabinovitch PS. SS-31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell. 2020 Oct;19(10):e13213. doi: 10.1111/acel.13213. Epub 2020 Aug 11. PMID: 32779818; PMCID: PMC7576234.