Probiotic microbes: Are their anti-melanogenicity and longevity promoting activities closely linked through the major "pathogenic" kinase PAK1?

Abstract

PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Interestingly, PAK1deficient mutant of melanocytes produces less melanin (only a half compared with the wild-type) in the presence of either serum (PDGF) or α-MSH (alpha-melanocyte stimulating hormone). These observations indicate that the major "pathogenic" kinase PAK1 is responsible for both shortening the healthy lifespan, and PDGF/α-MSH-dependent melanogenesis. For screening of PAK1-blocking probiotic bacteria or their products, their anti-melanogenic as well as longevity promoting properties were examined. Recently it was found that C. elegans fed with Lactobacillus rhamnosus in Xinjiang cheese lives 40% longer than the worm fed with the standard E. coli. Interestingly, a Chinese traditional medicine called "ChiBai" fermented with the Lactobacillus rhamnosus also inhibited the α-MSH-induced melanogenesis, and this bacteria itself produces butyric acid that blocks the oncogenic HDAC (histone deacetylase)-PAK1 signaling pathway. These findings strongly suggest, if not proven, that anti-melanogenic activity of Lactobacillus and many other probiotic bacteria might serve as a reliable indicator for their longevity promoting activity. In this context, a popular Japanese Lactobacillus-fermented milk drink called "Calpis", developed a century ago, and recently proven to inhibit the melanogenesis by suppressing the PAK1-dependent tyrosinase gene expression, may potentially prolong our healthy lifespan.