dwarf mice
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2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 456-456
Author(s):  
Holly M Brown-Borg

Abstract Aging is the major risk factor for many diseases but the mechanisms are poorly understood. The risk of developing hepatic steatosis increases with age and the health impact of this disease is negative and high. When challenged with high fat diets, long living Ames mice withstand the detrimental metabolic effects that occur in normal mice. We examined transcriptomic and epigenomic profiles of Ames and wild type hepatocytes in the presence or absence of fat to demonstrate that the epigenomic profile drives transcription factor and downstream gene expression resulting in susceptibility or resistance to fatty liver disease. We found that markers of steatosis are related to gene expression in wild type and Ames mice, and dwarf mice retain fewer lipid droplets compared to wild type mice. These studies will provide data to guide our understanding of mechanisms leading to hepatic disease and define factors that provide protection from age-related metabolic disorders.


Author(s):  
Yujun Liu ◽  
Michal M. Masternak ◽  
Augusto Schneider ◽  
Xu Zhi

GeroScience ◽  
2021 ◽  
Author(s):  
Rachana Trivedi ◽  
Bailey Knopf ◽  
Jitendra Kumar Tripathi ◽  
Shar Rakoczy ◽  
Gunjan D. Manocha ◽  
...  

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.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5034
Author(s):  
Eliana Rosa Lima ◽  
Claudia Regina Cecchi ◽  
Eliza Higuti ◽  
Gustavo Protasio Pacheco de Jesus ◽  
Alissandra Moura Gomes ◽  
...  

Previous non-viral gene therapy was directed towards two animal models of dwarfism: Immunodeficient (lit/scid) and immunocompetent (lit/lit) dwarf mice. The former, based on hGH DNA administration into muscle, performed better, while the latter, a homologous model based on mGH DNA, was less efficient, though recommended as useful for pre-clinical assays. We have now improved the growth parameters aiming at a complete recovery of the lit/lit phenotype. Electrotransfer was based on three pulses of 375 V/cm of 25 ms each, after mGH-DNA administration into two sites of each non-exposed tibialis cranialis muscle. A 36-day bioassay, performed using 60-day old lit/lit mice, provided the highest GH circulatory levels we have ever obtained for GH non-viral gene therapy: 14.7 ± 3.7 ng mGH/mL. These levels, at the end of the experiment, were 8.5 ± 2.3 ng/mL, i.e., significantly higher than those of the positive control (4.5 ± 1.5 ng/mL). The catch-up growth reached 40.9% for body weight, 38.2% for body length and 82.6%–76.9% for femur length. The catch-up in terms of the mIGF-1 levels remained low, increasing from the previous value of 5.9% to the actual 8.5%. Although a complete phenotypic recovery was not obtained, it should be possible starting with much younger animals and/or increasing the number of injection sites.


Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 176 ◽  
Author(s):  
Teresa G. Valencak ◽  
Tanja Spenlingwimmer ◽  
Ricarda Nimphy ◽  
Isabel Reinisch ◽  
Jessica M. Hoffman ◽  
...  

Laboratory mouse models with genetically altered growth hormone (GH) signaling and subsequent endocrine disruptions, have longer lifespans than control littermates. As such, these mice are commonly examined to determine the role of the somatotropic axis as it relates to healthspan and longevity in mammals. The two most prominent mouse mutants in this context are the genetically dwarf Ames and Snell models which have been studied extensively for over two decades. However, it has only been proposed recently that both white and brown adipose tissue depots may contribute to their delayed aging. Here we review the current state of the field and supplement it with recent data from our labs.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Allancer Divino De Carvalho Nunes ◽  
Lin Yu ◽  
Collin Lahde ◽  
Sarah Noureddine ◽  
Tatiana Saccon ◽  
...  

2020 ◽  
Vol 132 ◽  
pp. 110851 ◽  
Author(s):  
Tatiana Dandolini Saccon ◽  
Monique Tomazele Rovani ◽  
Driele Neske Garcia ◽  
Rafael Gianella Mondadori ◽  
Luis Augusto Xavier Cruz ◽  
...  

Physiology ◽  
2020 ◽  
Vol 35 (2) ◽  
pp. 96-111 ◽  
Author(s):  
Rochelle Buffenstein ◽  
Kaitlyn N. Lewis ◽  
Patrick A. Gibney ◽  
Vikram Narayan ◽  
Kelly M. Grimes ◽  
...  

Pedomorphy, maintenance of juvenile traits throughout life, is most pronounced in extraordinarily long-lived naked mole-rats. Many of these traits (e.g., slow growth rates, low hormone levels, and delayed sexual maturity) are shared with spontaneously mutated, long-lived dwarf mice. Although some youthful traits likely evolved as adaptations to subterranean habitats (e.g., thermolability), the nature of these intrinsic pedomorphic features may also contribute to their prolonged youthfulness, longevity, and healthspan.


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