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      NMDA RECEPTOR & FEAR
      January 16, 2021
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      INSULIN & MTOR
      February 8, 2021

      insulin & aging


      Reduced Circulating Insulin Enhances Insulin Sensitivity and Extends Lifespan


      The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+littermate controls, on a genetically stable Ins1null background. Proteomic and transcriptomicanalyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.


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      18. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression
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      20. Alcohol intake and insulin levels: the Normative aging Study
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      52. Human growth hormone and cortisol response to insulin stimulation in aging
      53. TGF-β and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance
      54. aging and the growth hormone/insulin like growth factor-I axis
      55. aging, synaptic dysfunction, and insulin-like growth factor (IGF)-1
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      67. Change of insulin action with aging in conscious rats determined by euglycemic clamp
      68. The role of insulin/IGF-like signaling in C. elegans longevity and aging
      69. Handgrip strength and insulin levels: cross-sectional and prospective associations in the Normative aging Study
      70. The demography of slow aging in male and female Drosophila mutant for the insulin‐receptor substrate homologue chico
      71. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila
      72. The enteric enhancement of glucose-stimulated insulin release: the role of GIP in aging, obesity, and non-insulin-dependent diabetes mellitus
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      76. Impairments in availability of insulin to liver in vivo and in binding of insulin to purified hepatic plasma membrane during aging
      77. Glucocorticoid effects on insulin-and IGF-I-regulated muscle protein metabolism during aging
      78. Estradiol, insulin-like growth factor-I and brain aging
      79. Circulating levels of insulin-like growth factor (IGF) binding protein-1 and-3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate …
      80. Adipocyte insulin resistance: effects of aging, obesity, exercise, and food restriction
      81. Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging
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      86. … serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like …
      87. The DAF‐2 insulin‐like signaling pathway independently regulates aging and immunity in C. elegans
      88. Reduction in the chondrocyte response to insulin‐like growth factor 1 in aging and osteoarthritis: studies in a non‐human primate model of naturally occurring disease
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      91. Effects of aging and sex on plasma insulin-like growth factor I (IGF-I) levels in normal adults
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      95. … decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging
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      98. … , blood pressure, and insulin resistance through cocoa flavanol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and aging …
      99. Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories
      100. insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination
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      102. Body size, insulin/IGF signaling and aging in the nematode Caenorhabditis elegans
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      120. Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans
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      122. Does aging intensify the insulin resistance of human obesity?
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      134. … on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging
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      148. Growth hormone/insulin-like growth factor-I axis in aging: a summary of a National Institutes of aging-Sponsored Symposium
      149. Oxidative aging and insulin receptor signaling
      150. Articular chondrocytes from aging rats respond poorly to insulin-like growth factor-1: an altered signaling pathway
      151. Chronic 17β-estradiol treatment improves skeletal muscle insulin signaling pathway components in insulin resistance associated with aging
      152. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies
      153. Growth hormone induces somatostatin and insulin-like growth factor I gene expression in the cerebral hemispheres of aging rats
      154. insulin Growth Factor‐I Inhibits Apoptosis in Hematopoietic: Progenitor Cells Implications in Thymic aginga
      155. A possible role for insulin in the altered capability for hepatic enzyme adaptation during aging
      156. The paradox of neuronal insulin action and resistance in the development of aging-associated diseases
      157. insulin is differentially related to cognitive decline and atrophy in Alzheimer’s disease and aging
      158. Impaired ventilatory function and elevated insulin levels in nondiabetic males: the Normative aging Study
      159. MCH−/− mice are resistant to aging-associated increases in body weight and insulin resistance
      160. LET‐60 RAS modulates effects of insulin/IGF‐1 signaling on development and aging in Caenorhabditis elegans
      161. Effect of aging on the sensitivity of growth hormone secretion to insulin-like growth factor-I negative feedback
      162. insulin resistance and aging: a cause or a protective response?
      163. Which anthropometric indices of regional adiposity are related to the insulin resistance of aging?
      164. Altered regulation of insulin secretion in isolated islets of different sizes in aging rats
      165. Aberrant insulin receptor signaling and amino acid homeostasis as a major cause of oxidative stress in aging
      166. Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle.
      167. Hostility and urine norepinephrine interact to predict insulin resistance: the VA Normative aging Study
      168. Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: the Baltimore Longitudinal Study of aging
      169. insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease
      170. Appendicular skeletal muscle mass and insulin resistance in an elderly Korean population: the Korean social life, health and aging project-health examination …
      171. insulin receptor kinase activity in rat adipocytes is decreased during aging
      172. Diet, not aging, causes skeletal muscle insulin resistance
      173. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes
      174. Interaction of multiplication stimulating activity/rat insulin-like growth factor II with skeletal muscle satellite cells during aging
      175. … gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat …
      176. insulin receptors in the brain cortex of aging mice
      177. aging enhances the insulin resistance in obesity through both receptor and postreceptor alterations
      178. Training-induced enhancement of insulin action in human skeletal muscle: the influence of aging
      179. Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice
      180. Intranasal insulin improves age-related cognitive deficits and reverses electrophysiological correlates of brain aging
      181. Changes in insulin receptor kinase with aging in rat skeletal muscle and liver
      182. Changes in protein, carbohydrate, and fat metabolism with aging: possible role of insulin
      183. Tissue‐specific insulin signaling in the regulation of metabolism and aging
      184. Effect of age and caloric restriction on insulin receptor binding and glucose transporter levels in aging rats
      185. Adipose tissue-derived tumor necrosis factor activity correlates with fat cell size but not insulin action in aging rats
      186. insulin resistance and depressive symptoms in middle-aged and elderly Chinese: findings from the Nutrition and Health of aging Population in China Study
      187. The role of the glucose transport system in the postreceptor defect in insulin action associated with human aging
      188. Metallothionein antagonizes aging‐induced cardiac contractile dysfunction: role of PTP1B, insulin receptor tyrosine phosphorylation and Akt
      189. Modulation of SIRT1-Foxo1 signaling axis by resveratrol: implications in skeletal muscle aging and insulin resistance
      190. Caloric restriction and insulin-like growth factors in aging and cancer
      191. insulin exposure controls the rate of mammalian aging
      192. aging and insulin resistance in a group of nonobese male volunteers
      193. The endothelium abridges insulin resistance to premature aging
      194. Metabolic effects of resveratrol in mammals-a link between improved insulin action and aging
      195. Effect of gender on insulin resistance associated with aging
      196. Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes
      197. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione
      198. aging and oxidative stress reduce the response of human articular chondrocytes to insulin‐like growth factor 1 and osteogenic protein 1
      199. Influence of cardiac‐specific overexpression of insulin‐like growth factor 1 on lifespan and aging‐associated changes in cardiac intracellular Ca2+ homeostasis …
      200. Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis
      201. insulin regulation in AhR-null mice: embryonic cardiac enlargement, neonatal macrosomia, and altered insulin regulation and response in pregnant and aging AhR …
      202. β cell aging markers have heterogeneous distribution and are induced by insulin resistance
      203. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8)
      204. Dissociation between metabolic and vascular insulin resistance in aging
      205. aging and Restriction of Dietary Calories Increases insulin Receptor mRNA, and aging Increases Glucocorticoid Receptor MRNA in the Liver of Female C3B10RF1 …
      206. Method of treating reduced insulin-like growth factor and bone loss associated with aging
      207. Regulation of insulin receptor mRNA splicing in rat tissues: effect of fasting, aging, and diabetes
      208. The ubiquitin ligase CHIP integrates proteostasis and aging by regulation of insulin receptor turnover
      209. Secretion of insulin during aging
      210. aging is associated with elevated muscle triglyceride content and increased insulin-stimulated fatty acid uptake
      211. insulin in aging and cancer: antidiabetic drug Diabenol as geroprotector and anticarcinogen
      212. Regulation of insulin secretion by glucose during aging
      213. Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets
      214. insulin Release in aging: Dynamic Response of Isolated Islets of Langerhans of the Rat to D-Glucose and D-Glycer aldehyde
      215. Serum insulin‐like growth factor‐1 binding proteins 1 and 2 and mortality in older adults: the Health, aging, and Body Composition Study
      216. Relationships between insulin-like growth hormone factor-I and estradiol in reproductive aging
      217. Loss of postprandial insulin sensitization during aging
      218. aging is associated with increased HbA1c levels, independently of glucose levels and insulin resistance, and also with decreased HbA1c diagnostic specificity
      219. Longevity pathways (mTOR, SIRT, insulin/IGF-1) as key modulatory targets on aging and neurodegeneration
      220. Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging
      221. The effect of aging on insulin signalling pathway is tissue dependent: central role of adipose tissue in the insulin resistance of aging
      222. aging does not affect the activation of the myocyte insulin-like growth factor-1 autocrine system after infarction and ventricular failure in Fischer 344 rats
      223. Effects of epinephrine on insulin secretion and action in humans: interaction with aging
      224. Restorative effect of intracerebroventricular insulin-like growth factor-I gene therapy on motor performance in aging rats
      225. Effects of aging on insulin synthesis and secretion. Differential effects on preproinsulin messenger RNA levels, proinsulin biosynthesis, and secretion of newly made …
      226. Increased expression of type 1 insulin-like growth factor receptor messenger RNA in rat hippocampal formation is associated with aging and behavioral impairment
      227. insulin/IGF-I and related signaling pathways regulate aging in nondividing cells: from yeast to the mammalian brain
      228. aging and insulin resistance: just say iNOS
      229. … and normal prostate aging: differences in types I and II 5 alpha-reductase and steroid hormone receptor messenger ribonucleic acid (mRNA) levels, but not in insulin …
      230. aging per se increases the susceptibility to free fatty acid–induced insulin resistance
      231. aging and insulin sensitivity: role of blood pressure and sympathetic nervous system activity
      232. Stress contributes to the development of central insulin resistance during aging: implications for Alzheimer’s disease
      233. L-type Ca2+ channel-insulin-like growth factor-1 receptor signaling impairment in aging rat skeletal muscle
      234. Rats with low brain angiotensinogen do not exhibit insulin resistance during early aging
      235. insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats
      236. insulin-like growth factor-I receptor densities in human frontal cortex and white matter during aging, in Alzheimer’s disease, and in Huntington’s disease
      237. Serum levels of insulin‐like growth factor 1 in subjects with osteoarthritis of the knee. Data from the baltimore longitudinal study of aging
      238. Parental imprinting regulates insulin-like growth factor signaling: a Rosetta Stone for understanding the biology of pluripotent stem cells, aging and …
      239. From lipodystrophy and insulin resistance to metabolic syndrome: HIV infection, treatment and aging
      240. aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats
      241. Glucose intolerance and insulin resistance with aging—studies on insulin receptors and post-receptor events
      242. aging is associated with myocardial insulin resistance and mitochondrial dysfunction
      243. … disruption of spermidine/spermine N1‐acetyltransferase gene maintain nearly normal tissue polyamine homeostasis but show signs of insulin resistance upon aging
      244. Synthesis-secretion coupling of insulin: effect of aging.
      245. … metabolic alterations in the hippocampus caused by insulin signalling dysfunction and its association with cognitive impairment during aging and Alzheimer’s disease …
      246. Effect of aging on the expression of peroxisome proliferator-activated receptor γ and the possible relation to insulin resistance
      247. Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging
      248. insulin exposure and unifying aging
      249. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity
      250. Dexamethasone-induced insulin resistance and pancreatic adaptive response in aging rats are not modified by oral vanadyl sulfate treatment
      251. insulin release in aging: studies on adenylate cyclase, phosphodiesterase, and protein kinase in isolated islets of Langerhans of the rat
      252. Effect of aging on the kinetic characteristics of the insulin receptor autophosphorylation in rat adipocytes
      253. Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I
      254. DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth
      255. insulin‐like growth factor‐I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
      256. Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow
      257. Dietary (−)-Epigallocatechin-3-gallate supplementation counteracts aging-associated skeletal muscle insulin resistance and fatty liver in senescence-accelerated …
      258. Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 levels in aging and age-associated diseases
      259. Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans
      260. Development of insulin resistance during aging: involvement of central processes and role of adipokines
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