Abstract 10574: Living with Sexual Partner Slowed Klotho Deficiency-Induced Heart Aging via Suppressing Renal Sodium-Phosphate Co-Transporters

Abstract

Background: Staying young at heart is a dream of many aged people. Sexuality is now generally considered beneficial for the overall health. It reduces the risk of a heart attack. However, while the concept of “sex improves health” has been demonstrated, the underlying mechanism remains poorly understood. Methods & Results: Klotho mutant homozygous (KL-/-) mice and age- and sex-matched wild-type (WT) mice were used. One male and one female mouse were co-housed from weaning and fed with low-phosphorus diet to reduce serum phosphate level. And the mice co-housing with the same gender were used as control. Body weight was measured weekly and lifespan was recorded. Heart function was measured by magnetic resonance imaging (MRI). Mice were sacrificed just before dying. Klotho-deficient mice demonstrated heart aging phenotype, as evidenced by cardiac remodeling and cardiac dysfunction. The compromised cardiac function was associated with increased oxidative stress, mitochondrial damage and myocyte apoptosis. We showed that hyperphosphatemia contributes to Klotho deficiency-induced cardiac damages. Interestingly, sexuality attenuated cardiac aging. Mechanistically, sex increased estrogen secretion, which decreased hyperphosphatemia through inhibition of renal tubular sodium-dependent phosphate (NaPi) co-transporters. Co-housing sexual partners also attenuated oxidative stress and myocyte apoptosis and improved mitochondrial function. Moreover, living with sexual partners extends the lifespan by 86.8% in KL(-/-) female mice and 38.7% in male mice. Conclusion: In the Klotho deficiency-induced aging model, sexuality improves heart aging and extends lifespan. This study demonstrated for the first time that living with sexual partners increases estrogen secretion which inhibits renal NaPi co-transporters leading to attenuation Klotho deficiency-induced hyperphosphatemia and heart aging.