scholarly journals Augmentation of the heat shock axis during exceptional longevity in Ames dwarf mice

GeroScience ◽  
2021 ◽  
Author(s):  
Rachana Trivedi ◽  
Bailey Knopf ◽  
Jitendra Kumar Tripathi ◽  
Shar Rakoczy ◽  
Gunjan D. Manocha ◽  
...  
Keyword(s):  
Heat Shock ◽  
Dna Binding ◽  
Regulatory Elements ◽  
Mrna Levels ◽  
Wild Type ◽  
Exceptional Longevity ◽  
Ames Dwarf Mice ◽  
Age Dependent ◽  
Ames Dwarf ◽  
Dwarf Mice

AbstractHow the heat shock axis, repair pathways, and proteostasis impact the rate of aging is not fully understood. Recent reports indicate that normal aging leads to a 50% change in several regulatory elements of the heat shock axis. Most notably is the age-dependent enhancement of inhibitory signals associated with accumulated heat shock proteins and hyper-acetylation associated with marked attenuation of heat shock factor 1 (HSF1)–DNA binding activity. Because exceptional longevity is associated with increased resistance to stress, this study evaluated regulatory check points of the heat shock axis in liver extracts from 12 months and 24 months long-lived Ames dwarf mice and compared these findings with aging wild-type mice. This analysis showed that 12M dwarf and wild-type mice have comparable stress responses, whereas old dwarf mice, unlike old wild-type mice, preserve and enhance activating elements of the heat shock axis. Old dwarf mice thwart negative regulation of the heat shock axis typically observed in usual aging such as noted in HSF1 phosphorylation at Ser307 residue, acetylation within its DNA binding domain, and reduction in proteins that attenuate HSF1–DNA binding. Unlike usual aging, dwarf HSF1 protein and mRNA levels increase with age and further enhance by stress. Together these observations suggest that exceptional longevity is associated with compensatory and enhanced HSF1 regulation as an adaptation to age-dependent forces that otherwise downregulate the heat shock axis.

scholarly journals Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

2008 ◽  
Vol 295 (5) ◽  
pp. H1882-H1894 ◽  
Author(s):  
Anna Csiszar ◽  
Nazar Labinskyy ◽  
Viviana Perez ◽  
Fabio A. Recchia ◽  
Andrej Podlutsky ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Ros Generation ◽  
No Production ◽  
Wild Type ◽  
Ames Dwarf Mice ◽  
Igf I ◽  
Ames Dwarf ◽  
Dwarf Mice ◽  
Vascular Oxidative Stress

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•− and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•− and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•− and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.

scholarly journals GH gene expression in the submaxillary gland in normal and Ames dwarf mice

2001 ◽  
Vol 169 (2) ◽  
pp. 389-396 ◽  
Author(s):  
A Perez-Romero ◽  
E Dialynas ◽  
F Salame ◽  
A Amores ◽  
L Vidarte ◽  
...  
Keyword(s):  
Southern Blot ◽  
Submaxillary Gland ◽  
Rt Pcr ◽  
Submaxillary Glands ◽  
Ames Dwarf Mice ◽  
Igf I ◽  
Ames Dwarf ◽  
Heart Blood ◽  
Two Parameters ◽  
Dwarf Mice

High local GH-releasing hormone (GHRH) levels are capable of inducing transdifferentiation in salivary cells to synthesize GH. However, the factors implicated in this process remain unknown. To study this subject, normal and Ames dwarf mice were implanted in the submaxillary gland with a slow release pellet releasing 21 microgram GHRH (1-29)-NH(2)/day for 2 months. Control animals received placebo pellets at the same site. After 60 days, heart blood was collected and submaxillary glands were removed. Circulating levels of GH and IGF-I were significantly decreased (P<0.05) in dwarf mice in comparison with controls, and GHRH treatment did not modify either of these two parameters. Controls carrying GHRH pellets showed a significantly higher GH content (P<0.05) in the submaxillary gland than the placebo-treated normal mice. There were no differences between the IGF-I concentrations of placebo- and GHRH-treated salivary tissue from normal mice. Analysis of GH mRNA by RT-PCR followed by Southern blot revealed that GH transcripts were present in the salivary gland samples carrying the placebo pellets in both normal and dwarf mice. The expression of GH was significantly (P<0.05) increased by the GHRH pellets in salivary tissue from normal mice, but not in submaxillary glands from dwarf mice. Pit-1 mRNA was not detected in the GHRH-treated glands of normal and dwarf mice by RT-PCR or by Southern blot. Using these highly sensitive methods, we have been able to detect the transcription of both GH and Pit-1 in pituitaries from Pit-1-deficient Ames dwarf mice. The present experiment demonstrates that salivary tissue synthesizes GH when it is exposed to the influence of GHRH. Both basal and GHRH-induced salivary GH expression appear to be independent of Pit-1.

scholarly journals The role of miR‐146a‐5p on insulin signaling and inflammation in adipose tissue of longliving Ames dwarf mice.

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Allancer Divino De Carvalho Nunes ◽  
Lin Yu ◽  
Collin Lahde ◽  
Sarah Noureddine ◽  
Tatiana Saccon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Signaling ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Dwarf Mice

scholarly journals A Novel Transcriptional Repressor, Rhit, Is Involved in Heat-Inducible and Age-Dependent Expression of Mpv17-Like Protein, a Participant in Reactive Oxygen Species Metabolism

2010 ◽  
Vol 30 (10) ◽  
pp. 2306-2315 ◽  
Author(s):  
Reiko Iida ◽  
Misuzu Ueki ◽  
Toshihiro Yasuda
Keyword(s):  
Reactive Oxygen Species ◽  
Transcriptional Regulation ◽  
Heat Shock ◽  
Binding Site ◽  
Reactive Oxygen ◽  
Regulatory Elements ◽  
Oxygen Species ◽  
Heat Shock Element ◽  
Positive Elements ◽  
Age Dependent

ABSTRACT Mpv17-like protein (M-LP) is a protein that has been suggested to be involved in the metabolism of reactive oxygen species. The two M-LP isoforms in mouse, M-LPS and M-LPL, are generated by the alternative usage of promoters. M-LPS is expressed exclusively in kidneys after the age of 6 weeks, whereas M-LPL is expressed ubiquitously. To elucidate the molecular basis of M-LPS expression, we searched for cis-regulatory elements in the promoter region of M-LPS and identified heat shock element half-sites as positive elements and a Tramtrack 69K (Ttk 69K) binding site as a negative element. Furthermore, we isolated a novel transcription repressor, Rhit (regulator of heat-induced transcription), that binds to the Ttk 69K binding site within the M-LPS promoter by DNA affinity chromatography and confirmed its participation in the transcriptional regulation of M-LPS by RNA interference (RNAi). Sequence analysis revealed that Rhit contains a KRAB (Krüppel-associated box) domain and a DNA-binding domain composed of eight C2H2-type zinc fingers. Interestingly, exposure to heat shock stress resulted in the upregulation of M-LPS expression concurrent with the downregulation of Rhit expression. Moreover, the age-dependent expression of M-LPS was inversely correlated with that of Rhit. These observations strongly suggest that Rhit acts as a repressor in the heat-induced and age-dependent transcriptional regulation of M-LPS.

A mutant androgen receptor from patients with Reifenstein syndrome: identification of the function of a conserved alanine residue in the D box of steroid receptors

1993 ◽  
Vol 13 (12) ◽  
pp. 7850-7858
Author(s):  
F Kaspar ◽  
H Klocker ◽  
A Denninger ◽  
A C Cato
Keyword(s):  
Androgen Receptor ◽  
Dna Binding ◽  
Steroid Receptors ◽  
Regulatory Elements ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Wild Type ◽  
Binding Studies ◽  
Mutant Receptor ◽  
Alanine Residue

Reifenstein syndrome is an eponymic term that describes partial androgen-insensitive disorders. Androgen receptor isolated from five patients with this syndrome contains a specific mutation in the DNA binding domain of the receptor. This mutation converts an alanine to a threonine at position 596 next to the zinc catenation site at the second finger. The threonine 596 mutant receptor mediated normal androgen response at promoters with closely positioned multiple regulatory elements for the androgen receptor and other transcription factors. Promoters with single isolated androgen response elements were not transactivated by the mutant receptor. In in vitro receptor-DNA binding studies, interaction with DNA by the mutant receptor was achieved only in the presence of an anti-androgen receptor antibody. Exchanging alanine 596 in the wild-type androgen receptor with serine or valine produced mutants with properties indistinguishable from those of the naturally occurring threonine 596 mutant receptor. These results indicate that an alanine residue at position 596 contributes important structural and functional activities to the androgen receptor. In the androgen receptor from the patients with Reifenstein syndrome, in which this alanine is converted to a threonine, wild-type receptor properties can be restored by exchanging an additional threonine at position 602 to an alanine. An alanine residue at position 596 or 602 in the DNA binding domain of the androgen receptor is therefore important for the full function of this receptor. In all steroid receptors that bind the core sequence AGAACANNNTGTTCT, an alanine residue is also present at a position equivalent to alanine 596 in the androgen receptor.

scholarly journals Primordial follicle reserve, DNA damage and macrophage infiltration in the ovaries of the long-living Ames dwarf mice

2020 ◽  
Vol 132 ◽  
pp. 110851 ◽  
Author(s):  
Tatiana Dandolini Saccon ◽  
Monique Tomazele Rovani ◽  
Driele Neske Garcia ◽  
Rafael Gianella Mondadori ◽  
Luis Augusto Xavier Cruz ◽  
...  
Keyword(s):  
Dna Damage ◽  
Primordial Follicle ◽  
Macrophage Infiltration ◽  
Ames Dwarf Mice ◽  
Ames Dwarf ◽  
Dwarf Mice
Sign in / Sign up

Export Citation Format

Share Document