About this Research Topic
In mammals, the fibroblast growth factor (FGF) family consists of 22 members that share a conserved core of approximately 120 amino acids with roughly 50% homology. Within this family are several subfamilies that can be distinguished predominantly by their mode of signaling. More specifically, there are intracrine/intracellular FGFs, as well as secreted FGFs with either paracrine or endocrine effects. It has long been known that FGFs play an essential role in mediating cellular longevity in vitro, and perhaps in vivo, via their effects on cellular function, especially proliferation, migration and differentiation. In vivo, paracrine FGFs are known to play a critical role in normal tissue development and maintenance, as well as wound healing and its related processes (e.g. angiogenesis).
More recently, the endocrine FGFs have been directly implicated in the regulation of organismal longevity secondary to their role in phosphate, calcium, Vitamin D and carbohydrate metabolism. Most significantly, increased expression of FGF21, a liver-derived FGF that is secreted during fasting, significantly extends the life span of mice. Moreover, FGF-receptor mediated signaling often involves a constitutive membrane-bound co-factor known as klotho that can also exist in a soluble form. This soluble (or secreted) form of klotho has widespread effects on oxidative stress, insulin/insulin-like growth factor axis signaling and cytokine expression (e.g. tumor necrosis factor-α; TNF-α) and ion homeostasis via the regulation of various ion channels and transporters, as well as the regulation cell surface protein turnover via its β-glucuronidase activity. Importantly, klotho hypomorphic mice exhibit a phenotype that is consistent with accelerated aging, while klotho overexpression extends longevity.
The proposed Research Topic, "FGF Family Proteins and Mammalian Aging", will explore the connections between circulating FGFs, FGF signaling pathways and cellular aging in the regulation of mammalian aging in the form of Original Research, Review, and Mini-Review Articles.
Specific topics to be covered include:
• Nutrition, FGF-21 and aging; especially in the context of both dietary and caloric restriction
• FGF-21, nutrition and the geometric framework
• FGF-21 and diabetes
• FGFs and stem cell dynamics
• FGFs and telomeres
• FGF-23 and brain aging
• The role of klotho in renal aging and pathology
• FGFs and mammalian longevity
• FGFs and tissue regeneration
• FGF-21, exercise and metabolism
Keywords: Aging, FGF, Klotho, Senescence, Metabolism