TY - JOUR
T1 - Role of hypothalamus in aging and its underlying cellular mechanisms
AU - Kim, Keetae
AU - Choe, Han Kyoung
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/1
Y1 - 2019/1
N2 - Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively. The underlying cellular mechanism for the hypothalamus-mediated aging progression comprises dysregulation of nutrient sensing, altered intercellular communication, stem cell exhaustion, loss of proteostasis, and epigenetic alterations. Furthermore, mammalian target of rapamycin (mTOR), NF-kB, hypothalamic stem cell, autophagy, and SIRT1 have been recognized as critical factors or pathways mediating the mechanism. Perhaps, further dissection of these pathways or components could provide the potential for developing a therapeutic intervention for age-related diseases or the extension of healthy lifespan.
AB - Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively. The underlying cellular mechanism for the hypothalamus-mediated aging progression comprises dysregulation of nutrient sensing, altered intercellular communication, stem cell exhaustion, loss of proteostasis, and epigenetic alterations. Furthermore, mammalian target of rapamycin (mTOR), NF-kB, hypothalamic stem cell, autophagy, and SIRT1 have been recognized as critical factors or pathways mediating the mechanism. Perhaps, further dissection of these pathways or components could provide the potential for developing a therapeutic intervention for age-related diseases or the extension of healthy lifespan.
KW - Aging
KW - Hypothalamus
KW - Mechanisms
UR - http://www.scopus.com/inward/record.url?scp=85046774500&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2018.04.008
DO - 10.1016/j.mad.2018.04.008
M3 - Review article
C2 - 29729230
AN - SCOPUS:85046774500
SN - 0047-6374
VL - 177
SP - 74
EP - 79
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
ER -