scholarly journals Adult-Onset Growth Hormone and Insulin-Like Growth Factor I Deficiency Reduces Neoplastic Disease, Modifies Age-Related Pathology, and Increases Life Span

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2920-2932 ◽  
Author(s):  
William E. Sonntag ◽  
Christy S. Carter ◽  
Yuji Ikeno ◽  
Kari Ekenstedt ◽  
Cathy S. Carlson ◽  
...  
Keyword(s):  
Life Span ◽  
Intracranial Hemorrhage ◽  
Cartilage Degeneration ◽  
Neoplastic Disease ◽  
Adult Onset ◽  
Functional Impairments ◽  
Tissue Degeneration ◽  
Age Related ◽  
Maximal Life Span ◽  
Igf I

Abstract Disruption of the insulin/IGF-I pathway increases life span in invertebrates. However, effects of decreased IGF-I signaling in mammalian models remain controversial. Using a rodent model with a specific and limited deficiency of GH and IGF-I, we report that GH and IGF-I deficiency throughout life [GH deficiency (GHD)] has no effect on life span compared with normal, heterozygous animals. However, treatment of GHD animals with GH from 4–14 wk of age [adult-onset (AO) GHD] increased median and maximal life span by 14% and 12%, respectively. Analysis of end-of-life pathology indicated that deficiency of these hormones decreased tumor incidence in GHD and AO-GHD animals (18 and 30%, respectively) compared with heterozygous animals and decreased the severity of, and eliminated deaths from, chronic nephropathy. Total disease burden was reduced by 24% in GHD and 16% in AO-GHD animals. Interestingly, the incidence of intracranial hemorrhage increased by 154 and 198% in GHD and AO-GHD animals, respectively, compared with heterozygous animals. Deaths from intracranial hemorrhage in AO-GHD animals were delayed by 14 wk accounting for the increased life span compared with GHD animals. The presence of GH and IGF-I was necessary to maximize reproductive fitness and growth of offspring early in life and to maintain cognitive function and prevent cartilage degeneration later in life. The diverse effects of GH and IGF-I are consistent with a model of antagonistic pleiotropy and suggest that, in response to a deficiency of these hormones, increased life span is derived at the risk of functional impairments and tissue degeneration.

III. Senescent enteric nervous system: lessons from extraintestinal sites and nonmammalian species

2002 ◽  
Vol 283 (5) ◽  
pp. G1020-G1026 ◽  
Author(s):  
John W. Wiley
Keyword(s):  
Life Span ◽  
Cellular Function ◽  
Colonic Transit ◽  
Advanced Age ◽  
Physiological Aging ◽  
Functional Changes ◽  
Age Related ◽  
Igf I ◽  
And Function ◽  
Kinase Expression

Functional changes in GI motility associated with advanced age include slowing of gastric emptying, decreased peristalsis, and slowing of colonic transit. These changes appear to be associated with region-specific loss of neurons and impaired function. The mechanism(s) underlying physiological aging are likely to be multifactorial. Alterations in specific signal transduction pathways have been reported at the level of the receptor and postreceptor events including kinase expression and function, mitochondrial function, and activation of the apoptosis cascade. Advanced age is associated with increased oxidative stress and its concomitant effects on cellular function. Whereas no specific genes have been causally linked to life span in mammals, studies involving nonmammalian species suggest that specific genes are involved in determining life span and age-related changes in cellular function. Caloric restriction is the only intervention shown to slow aging in a variety of species. Recent studies implicate a possible role for an insulin/IGF-I cascade in the region- and tissue-specific changes associated with physiological aging.

Saccharomyces cerevisiae SSD1-VConfers Longevity by a Sir2p-Independent Mechanism

Genetics ◽  
2004 ◽  
Vol 166 (4) ◽  
pp. 1661-1672 ◽  
Author(s):  
Matt Kaeberlein ◽  
Alex A Andalis ◽  
Gregory B Liszt ◽  
Gerald R Fink ◽  
Leonard Guarente
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Life Span ◽  
Cell Cycle Progression ◽  
Polymorphic Locus ◽  
Cell Integrity ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Maximal Life Span ◽  
Independent Mechanism ◽  
Yeast Aging

AbstractThe SSD1 gene of Saccharomyces cerevisiae is a polymorphic locus that affects diverse cellular processes including cell integrity, cell cycle progression, and growth at high temperature. We show here that the SSD1-V allele is necessary for cells to achieve extremely long life span. Furthermore, addition of SSD1-V to cells can increase longevity independently of SIR2, although SIR2 is necessary for SSD1-V cells to attain maximal life span. Past studies of yeast aging have been performed in short-lived ssd1-d strain backgrounds. We propose that SSD1-V defines a previously undescribed pathway affecting cellular longevity and suggest that future studies on longevity-promoting genes should be carried out in long-lived SSD1-V strains.

scholarly journals Positive Emodiversity Buffers the Association Between Stress and Depressive Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 653-653
Author(s):  
Lizbeth Benson ◽  
Anthony Ong
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Life Span ◽  
Daily Diary ◽  
National Study ◽  
Younger Adults ◽  
Shannon's Entropy ◽  
Daily Experiences ◽  
Age Related ◽  
Optimal Functioning

Abstract Intensive measurements of individuals’ experiences allow for identifying patterns of functioning that may be markers of resilience, and whether such patterns differ across the life span. Using 8 daily diary reports collected in the second burst of the National Study of Daily Experiences (NSDE, n=848, age 34-84; 55%female), we examined whether positive emodiversity (Shannon’s entropy) attenuated the association between cumulative stressor exposure and depressive symptoms, and age-related differences therein. Results indicated age moderated the extent to which positive emodiversity attenuated the association between stress and depressive symptoms (b=0.11, p < .05). The attenuated association was strongest for younger adults with higher positive emodiversity, compared to those with lower positive emodiversity. For older adults, the association between stress and depressive symptoms was relatively similar regardless of their positive emodiversity. Implications pertain to for whom and in what contexts specific types of dynamic emotion experiences may promote optimal functioning and resilience.

The interrelationship between and the regulation of hepatic growth hormone receptors and circulating GH binding protein in the pig

1992 ◽  
Vol 126 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Geoffrey R Ambler ◽  
Bernhard H Breier ◽  
Andrzej Surus ◽  
Hugh T Blair ◽  
Stuart N McCutcheon ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Binding Capacity ◽  
Binding Protein ◽  
Somatic Growth ◽  
Gh Receptor ◽  
Age Related ◽  
Igf I ◽  
Serum Gh

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.

scholarly journals Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice

2021 ◽  
Vol 22 (7) ◽  
pp. 3548
Author(s):  
Kenji Watanabe ◽  
Shuichi Shibuya ◽  
Yusuke Ozawa ◽  
Toshihiko Toda ◽  
Takahiko Shimizu
Keyword(s):  
Apoptotic Cell ◽  
Oxygen Species ◽  
Double Knockout ◽  
In Vivo Experiments ◽  
P53 Signaling ◽  
Tissue Degeneration ◽  
Age Related ◽  
Tissue Changes ◽  
P53 Activation

Intracellular superoxide dismutases (SODs) maintain tissue homeostasis via superoxide metabolism. We previously reported that intracellular reactive oxygen species (ROS), including superoxide accumulation caused by cytoplasmic SOD (SOD1) or mitochondrial SOD (SOD2) insufficiency, induced p53 activation in cells. SOD1 loss also induced several age-related pathological changes associated with increased oxidative molecules in mice. To evaluate the contribution of p53 activation for SOD1 knockout (KO) (Sod1−/−) mice, we generated SOD1 and p53 KO (double-knockout (DKO)) mice. DKO fibroblasts showed increased cell viability with decreased apoptosis compared with Sod1−/− fibroblasts. In vivo experiments revealed that p53 insufficiency was not a great contributor to aging-like tissue changes but accelerated tumorigenesis in Sod1−/− mice. Furthermore, p53 loss failed to improve dilated cardiomyopathy or the survival in heart-specific SOD2 conditional KO mice. These data indicated that p53 regulated ROS-mediated apoptotic cell death and tumorigenesis but not ROS-mediated tissue degeneration in SOD-deficient models.

scholarly journals Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study

2007 ◽  
Vol 292 (1) ◽  
pp. E353-E358 ◽  
Author(s):  
Marcello Maggio ◽  
Fulvio Lauretani ◽  
Gian Paolo Ceda ◽  
Stefania Bandinelli ◽  
Shehzad Basaria ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Older Women ◽  
Inflammatory Markers ◽  
Hormone Replacement ◽  
Sex Hormone Binding Globulin ◽  
Bilateral Oophorectomy ◽  
Age Related ◽  
Increased Risk ◽  
Igf I

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (≥65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone ( P < 0.001), IL-6 ( P < 0.001), CRP ( P < 0.001), and HOMA ( P < 0.001) and lower levels of SHBG ( P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS ( P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21–0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.

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