title: Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging.
abstract: The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.
authors.affiliation: Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Rm. 107, Louisville, KY, 40202, USA. mzrata01@louisville.edu.|Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland. mzrata01@louisville.edu.
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.affiliation: Geriatrics Research, Department of Internal Medicine and Physiology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.affiliation: Brander Cancer Research Institute and Department of Pathology, New York Medical College, Valhalla, NY, USA.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Darzynkiewicz
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D007328:Insulin; D013002:Somatomedins; D019382:Human Growth Hormone
keywords: Aging; Geroprevention; Growth hormone; HSCs; Insulin; Insulin-like growth factor; Longevity; Parental imprinting; VSELs