scholarly journals Multi-omic rejuvenation and lifespan extension upon exposure to youthful circulation

2021 ◽  
Author(s):  
Bohan Zhang ◽  
David E Lee ◽  
Alexandre Trapp ◽  
Alexander Tyshkovskiy ◽  
Ake T Lu ◽  
...  
Keyword(s):  
Physiological Parameters ◽  
Biological Age ◽  
Intermediate Phenotype ◽  
Lifespan Extension ◽  
Mouse Tissues ◽  
Clock Models

Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on the biological age of organisms and their long-term health remains unknown. Here, we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the biological age of blood and liver based on epigenetic analyses across several clock models on two independent platforms; remarkably, this rejuvenation effect persisted even after 2 months of detachment. Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a comprehensive multi-omic rejuvenation effect. In addition, old HPB mice showed transcriptome changes opposite to aging, but akin to several lifespan-extending interventions. Altogether, we reveal that long-term HPB can decrease the biological age of mice, in part through long-lasting epigenetic and transcriptome remodeling, culminating in the extension of lifespan and healthspan.

scholarly journals Chronic Exposure to Youthful Circulation Leads to Epigenetic Reprogramming and Lifespan Extension

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 682-682
Author(s):  
Bohan Zhang ◽  
David Lee ◽  
Alexander Tyshkovskiy ◽  
Akshay Bareja ◽  
Csaba Kerepesi ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Aging Process ◽  
Biological Age ◽  
Biological Aging ◽  
Lifespan Extension ◽  
Molecular Signatures ◽  
Signature Analysis ◽  
Rna Seq ◽  
Aging Research

Abstract Heterochronic parabiosis is a powerful rejuvenation model in aging research. Due to limitations in the duration of blood sharing and/or physical attachment, it is currently unclear if parabiosis retards the molecular signatures of aging or affects healthspan/lifespan in the mouse. Here, we describe a long-term heterochronic parabiosis model, which appears to slow down the aging process. We observed a “deceleration” of biological age based on molecular aging biomarkers estimated with DNA methylation clock and RNA-seq signature analysis. The slowing of biological aging was accompanied by systemic amelioration of aging phenotypes. Consistent with these findings, we found that aged mice, which underwent heterochronic parabiosis, had an increased healthspan and lifespan. Overall, our study re-introduces a prolonged parabiosis and detachment model as a novel rejuvenation therapy, suggesting that a systemic reset of biological age in old organisms can be achieved through the exposure to young environment.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2021 ◽  
Vol 288 (1950) ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Dietary Restriction ◽  
Mortality Risk ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
Negative Effects ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

Dietary restriction (DR) increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here, we investigated the effect of DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in Caenorhabditis elegans . We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P 0 ), it has a wide range of both positive and negative effects on their descendants (F 1 –F 3 ). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F 3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

scholarly journals Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

2020 ◽  
Author(s):  
Edward R. Ivimey-Cook ◽  
Kris Sales ◽  
Hanne Carlsson ◽  
Simone Immler ◽  
Tracey Chapman ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Mortality Risk ◽  
Future Generations ◽  
Lifespan Extension ◽  
Dietary Interventions ◽  
C Elegans ◽  
Trade Offs ◽  
Wide Range ◽  
Broad Variety

AbstractDietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

DMAPT is an Effective Radioprotector from Long-Term Radiation-Induced Damage to Normal Mouse Tissues In Vivo

2019 ◽  
Vol 192 (2) ◽  
pp. 231 ◽  
Author(s):  
Katherine L. Morel ◽  
Rebecca J. Ormsby ◽  
Sonja Klebe ◽  
Christopher J. Sweeney ◽  
Pamela J. Sykes
Keyword(s):  
Normal Mouse ◽  
Mouse Tissues ◽  
Radiation Induced

Storage Levels of Ddt Metabolites in Mouse Tissues following Long Term Exposure to Technical DDT

1971 ◽  
Vol 57 (6) ◽  
pp. 377-396 ◽  
Author(s):  
Lorenzo Tomatis ◽  
Vladimir Turusov ◽  
Benedetto Terracini ◽  
Nicholas Day ◽  
William F. Barthel ◽  
...  
Keyword(s):  
Reproductive Organs ◽  
Whole Body ◽  
Fat Tissue ◽  
Strong Negative Correlation ◽  
Pregnant Females ◽  
Mouse Tissues ◽  
Term Administration ◽  
Liver And Kidney ◽  
Dose Levels

The storage levels of DDT and its metabolites, following the long term administration of technical DDT at the dose levels of 2, 20, 50 and 250 ppm to mice, were evaluated in the fat tissue, liver, kidney, brain and reproductive organs. In addition, storage levels were evaluated in foetuses and newborns of DDT-treated mothers. Apart from op'-DDT, there was a direct relationship between the concentration of each metabolite in each organ and the dose to which the animal was exposed. The highest concentration of DDT and metabolites was found in the fat tissue followed by reproductive organs, liver and kidney together, and lastly brain. The most prevalent metabolite was pp'-DDT, except in the liver, where pp'-DDD showed the highest concentration. Pregnant females had lower concentrations of all metabolites than non-pregnant females. The concentration of residues in samples of total foetal litters was directly related to the concentration of DDT fed to the mother. There was a strong negative correlation between the concentration of pp'-DDT and that of pp'-DDD in the foetuses and the placentas of the same litter. A significant increase in whole body DDT concentration was observed shortly after birth.

scholarly journals Endocrine and Physiological Changes in Response to Chronic Corticosterone: A Potential Model of the Metabolic Syndrome in Mouse

2010 ◽  
Vol 31 (2) ◽  
pp. 261-261
Author(s):  
Ilia N. Karatsoreos ◽  
Sarah M. Bhagat ◽  
Nicole P. Bowles ◽  
Zachary M. Weil ◽  
Donald W. Pfaff ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Experimental Studies ◽  
Intermediate Phenotype ◽  
Physiological Changes ◽  
The Metabolic Syndrome ◽  
Changes In Risk ◽  
High Doses ◽  
And Behavior ◽  
Plasma Leptin

ABSTRACT Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term effects, long-term CORT exposure can result in damage to the physiological systems it protects acutely. Disruption of this important physiologic signal is observed in numerous disparate disorders, ranging from depression to Cushing’s syndrome. Thus, understanding the effects of chronic high CORT on metabolism and physiology is of key importance. We explored the effects of 4-wk exposure to CORT dissolved in the drinking water on the physiology and behavior of male mice. We used this approach as a noninvasive way of altering plasma CORT levels, whereas retaining some integrity in the diurnal rhythm present in normal animals. This approach has advantages over methods involving constant CORT pellets, CORT injections, or adrenalectomy. We found that high doses of CORT (100 μg/ml) result in rapid and dramatic increases in weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, hyperphagia, and decreased home-cage locomotion. A lower dose of CORT (25 μg/ml) resulted in an intermediate phenotype in some of these measures, whereas having no effect on others. We propose that the physiological changes observed in the high-CORT animals approximate changes observed in individuals suffering from the metabolic syndrome and that they potentially serve as a model for hypercortisolemia and stress-related obesity.

scholarly journals Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals

2015 ◽  
Author(s):  
Xun Lan ◽  
Jonathan K. Pritchard
Keyword(s):  
Gene Expression ◽  
Gene Dosage ◽  
Functional Adaptation ◽  
Small Scale ◽  
Loss Of Function ◽  
Whole Genome Duplications ◽  
Mouse Tissues ◽  
Genome Duplications ◽  
Key Factor

AbstractGene duplication is a fundamental process in genome evolution. However, most young duplicates are degraded into pseudogenes by loss-of-function mutations, and the factors that allow some duplicate pairs to survive long-term remain controversial. One class of models to explain duplicate retention invokes sub- or neofunctionalization, especially through evolution of gene expression, while other models focus on sharing of gene dosage. While studies of whole genome duplications tend to support dosage sharing, the primary mechanisms in mammals–where duplications are small-scale and thus disrupt dosage balance– are unclear. Using RNA-seq data from 46 human and 26 mouse tissues we find that sub-functionalization of expression evolves slowly, and is rare among duplicates that arose within the placental mammals. A major impediment to subfunctionalization is that tandem duplicates tend to be co-regulated by shared genomic elements, in contrast to the standard assumption of modularity of gene expression. Instead, consistent with the dosage-sharing hypothesis, most young duplicates are down-regulated to match expression of outgroup singleton genes. Our data suggest that dosage sharing of expression is a key factor in the initial survival of mammalian duplicates, followed by slower functional adaptation enabling long-term preservation.

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