The use of a bioactive peptide derived from edible Chinese yam to reduce chronic inflammation (inflammaging) in aging ovaries.

Normal ovarian aging results in ovarian follicle and estrogen reduction, oocyte quality deterioration, and ovarian tissue degeneration. Ovarian aging not only is one of the causes of the onset of menopause, but it also leads to an increased risk of developing several life-threatening diseases, such as brittle bone disease, impaired cognitive function, and cardiovascular disease. This has not only adversely affected the quality of life, but also caused an economic burden on the Hong Kong Hospital Authority. Despite this, the mechanism of ovarian aging is still largely unknown. The only treatment option currently available to alleviate menopausal symptoms and prevent related diseases is hormone replacement therapy (HRT), but the number of women taking HRT has dropped dramatically after 2002 due to safety concerns. Prolongation of ovarian lifespan by edible, safer and affordable natural products offers a new treatment strategy for delaying/ preventing such life-threatening diseases, addressing the safety concerns of HRT, and supports the long-term goal of this project.

Cellular chronic inflammation and reactive nitrogen species-mediated cellular death are the key aging features in living organisms, also known as “inflammaging”. Specifically, the production of age-related NF-κB inflammatory mediators, including serum IL-6, peripheral blood mononuclear cell cytokines (TNFα and IL-1β), and iNOS- induced free radicals (i.e., reactive nitrogen species), increases with aging in women. Edible Chinese yam extract is effective in mitigating the menopausal syndrome clinically via increasing serum estradiol level. Recently, we published and licensed a US patent for discovery of the estradiol-stimulating and osteogenic protein derived from edible Chinese yam, namely DOI, with molecular weight of 33.5-kDa, which could increase serum estradiol levels via translational up-regulation of ovarian aromatase, but not breast aromatase. Also, since it did not stimulate the proliferation of breast and ovarian cancers, it may be a potential safer alternative of HRT. Our current pilot study in a well-characterized naturally aging female SD-rat model revealed that DOI suppressed the NF-κB inflammatory mediators and increased anti-oxidative factors in aging rat ovaries. Besides, one of its synthetic tryptic peptides with the highest estradiol-stimulating potency has been identified; it warrants a full scale study to confirm the findings, to examine its effects on reducing chronic inflammation in aging ovaries, and to study its effect on ovarian lifespan prolongation. The proposed investigation will further explore the added-values of the patented DOI by studying the DOI-derived peptide for extension of ovarian lifespan. As the global population of post- menopausal women will reach 1.2 billion by 2030; our study will benefit these individuals worldwide.