Once spores of the probiotic bacterium B. subtilis are
incorporated in the diet and consumed, they survive the transit through the
stomach and reach the human intestine (Left cartoon). These gut
spores germinate and the active form of the probiotic (vegetative cells of
B. subtilis) emerges, multiples and forms a beneficial
biofilm in the host intestine (Bottom cartoon). Biofilm B.
subtilis cells produce a continued and coordinated provision of
beneficial and anti-aging NO and CSF molecules to the host tissues (bottom and
right cartoons). At genetic level, longevity is regulated by the activity of the
gene-transcription factors FOXO and HSF (Right cartoon). The
binding of insulin-like molecules activates insulin receptor which in turn
activates a series of protein kinase enzymes that phosphorylate FOXO, keeping it
inactive in the cytoplasm. Additionally, active insulin receptor is responsible
for the formation of an inhibitory protein complex that sequesters HSF in the
cytoplasm. Beneficial signals (NO, CSF and others) derived from the biofilm
established by B. subtilis produce a direct or indirect
(through DR activation) downregulation of insulin receptor (Right
cartoon). Upon downregulation of the insulin receptor, FOXO and HSF
become active in the nucleus. There, both prolongevity transcription factors
orchestrate the activation of host genes responsible for (i) resistance to
age-related diseases and (ii) a prolonged and healthy longevity. Symbols: (red)
repression, (green) activation.