東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Investigating the Role of Cellular S...

Shigdar, Shahjahan Miah.

Linked to FindBook

Google Book

Amazon

博客來

Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia./
Author:	Shigdar, Shahjahan Miah.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	301 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
Contained By:	Dissertations Abstracts International83-06B.
Subject:	Adenosine. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28871421
ISBN:	9798759927310

Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia.
Shigdar, Shahjahan Miah.

Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 301 p.

Source: Dissertations Abstracts International, Volume: 83-06, Section: B.

Thesis (Ph.D.)--The University of Liverpool (United Kingdom), 2021.

Senescence was first described by the pioneering work of Hayflick whereby human diploid fibroblasts underwent repeated population doublings, and the cells demonstrated a finite replicative limit in culture. It is now recognised that most replicative cells have the capability to undergo senescence. More recently senescence-like properties have been described in terminally differentiated cells, including skeletal muscle, although the nature of this senescence remains unclear. There is limited data examining the role of senescence in the determination of terminally differentiated tissues such as skeletal muscle.The overall hypothesis of this thesis was that senescent cells accumulate in old mice, either locally to skeletal muscle or distally, and that they produce an inflammatory Senescence Associated Secretory Phenotype (SASP) which may contribute at least in part to the chronic NF-κB activation and the loss of muscle mass and function seen in the muscles of old compared with adult wild type (WT) mice. This programme of work tested this hypothesis by utilising different models of senescence in vitro and in vivo and using a senolytic and transgenic intervention.Initial studies examined the potential for mouse skeletal muscle myoblasts (C2C12 myoblasts) to undergo senescence when treated with the DNA damaging agent, etoposide. Treatment of cells with etoposide resulted in cell cycle arrest, increased levels of p21, increased SA-β-Gal activity, and altered morphology, providing proof-of-principle that mononuclear myoblasts can become senescent. Further, the senescent myoblasts produced a proinflammatory SASP detectable in the cell media that was able to increase NF-κB transcription factor activity in mature C2C21 myotubes. Interpretation and comparison of data from senescent cells and control cells proved a challenge since under normal conditions, control myoblasts continue to divide until reaching confluence and contact inhibition occurs. At this point muscle cells initiate differentiation, with expression of some indices common to senescence.Examination of muscles of old WT mice showed no evidence of the presence of classical senescent cells in muscles of old mice although old mice showed evidence of increased levels of cytokines and chemokines in the plasma. Data suggest that muscle may partially contribute to the increase in some of these plasma cytokines/chemokines by a non-senescent mechanism. In support of this conclusion, studies using either a transgenic or a pharmacological approach to remove whole body senescent cells in old mice had some minor effects on plasma cytokine/chemokine levels but provided no protection against the age-related loss of muscle mass and function.Evidence for the presence of senescence cells in old mice remains unclear but some studies have suggested that removal of senescent cells provides protection against age-related muscle loss. One potential reason for the difference with the current study is the age of the mice used whereby studies that have demonstrated senescence within skeletal muscle have commonly made use of geriatric (32-months-old) mice suggesting that senescence is only involved in the very late stages of sarcopenia.

ISBN: 9798759927310Subjects--Topical Terms:

1362513
Adenosine.

Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia.
LDR:04547nmm a2200469 4500 001 2401211
005 20241022112104.5
006 m o d
007 cr#unu||||||||
008 251215s2021 ||||||||||||||||| ||eng d
020 $a 9798759927310
035 $a (MiAaPQ)AAI28871421
035 $a (MiAaPQ)Liverpool_3134929
035 $a AAI28871421
035 $a 2401211
040 $a MiAaPQ $c MiAaPQ
100 1 $a Shigdar, Shahjahan Miah. $3 3771292
245 1 0 $a Investigating the Role of Cellular Senescence in Skeletal Muscle and Sarcopenia.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 301 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-06, Section: B.
500 $a Advisor: McArdle, Anne;Vasilaki, Aphordite;Staunton, Caroline.
502 $a Thesis (Ph.D.)--The University of Liverpool (United Kingdom), 2021.
520 $a Senescence was first described by the pioneering work of Hayflick whereby human diploid fibroblasts underwent repeated population doublings, and the cells demonstrated a finite replicative limit in culture. It is now recognised that most replicative cells have the capability to undergo senescence. More recently senescence-like properties have been described in terminally differentiated cells, including skeletal muscle, although the nature of this senescence remains unclear. There is limited data examining the role of senescence in the determination of terminally differentiated tissues such as skeletal muscle.The overall hypothesis of this thesis was that senescent cells accumulate in old mice, either locally to skeletal muscle or distally, and that they produce an inflammatory Senescence Associated Secretory Phenotype (SASP) which may contribute at least in part to the chronic NF-κB activation and the loss of muscle mass and function seen in the muscles of old compared with adult wild type (WT) mice. This programme of work tested this hypothesis by utilising different models of senescence in vitro and in vivo and using a senolytic and transgenic intervention.Initial studies examined the potential for mouse skeletal muscle myoblasts (C2C12 myoblasts) to undergo senescence when treated with the DNA damaging agent, etoposide. Treatment of cells with etoposide resulted in cell cycle arrest, increased levels of p21, increased SA-β-Gal activity, and altered morphology, providing proof-of-principle that mononuclear myoblasts can become senescent. Further, the senescent myoblasts produced a proinflammatory SASP detectable in the cell media that was able to increase NF-κB transcription factor activity in mature C2C21 myotubes. Interpretation and comparison of data from senescent cells and control cells proved a challenge since under normal conditions, control myoblasts continue to divide until reaching confluence and contact inhibition occurs. At this point muscle cells initiate differentiation, with expression of some indices common to senescence.Examination of muscles of old WT mice showed no evidence of the presence of classical senescent cells in muscles of old mice although old mice showed evidence of increased levels of cytokines and chemokines in the plasma. Data suggest that muscle may partially contribute to the increase in some of these plasma cytokines/chemokines by a non-senescent mechanism. In support of this conclusion, studies using either a transgenic or a pharmacological approach to remove whole body senescent cells in old mice had some minor effects on plasma cytokine/chemokine levels but provided no protection against the age-related loss of muscle mass and function.Evidence for the presence of senescence cells in old mice remains unclear but some studies have suggested that removal of senescent cells provides protection against age-related muscle loss. One potential reason for the difference with the current study is the age of the mice used whereby studies that have demonstrated senescence within skeletal muscle have commonly made use of geriatric (32-months-old) mice suggesting that senescence is only involved in the very late stages of sarcopenia.
590 $a School code: 0722.
650 4 $a Adenosine. $3 1362513
650 4 $a Ontology. $3 530874
650 4 $a Cancer therapies. $3 3557730
650 4 $a DNA damage. $3 916185
650 4 $a Cytokines. $3 687114
650 4 $a Chronic illnesses. $3 3550688
650 4 $a Biology. $3 522710
650 4 $a Epigenetics. $3 1568224
650 4 $a Polymerase chain reaction. $3 518049
650 4 $a Genotype & phenotype. $3 3561790
650 4 $a Genes. $3 600676
650 4 $a Apoptosis. $3 600650
650 4 $a Kinases. $3 3558077
650 4 $a Cell cycle. $3 766119
650 4 $a Cell culture. $3 604671
650 4 $a Musculoskeletal system. $3 548825
650 4 $a Aging. $3 543123
650 4 $a Cyclin-dependent kinases. $3 868634
650 4 $a Genetic engineering. $3 530509
650 4 $a Chromosomes. $3 638948
650 4 $a Phosphorylation. $3 816803
650 4 $a Morphology. $3 591167
650 4 $a Biochemistry. $3 518028
650 4 $a Bioengineering. $3 657580
650 4 $a Cellular biology. $3 3172791
650 4 $a Chemistry. $3 516420
650 4 $a Engineering. $3 586835
650 4 $a Genetics. $3 530508
650 4 $a Gerontology. $3 533633
650 4 $a Immunology. $3 611031
650 4 $a Medicine. $3 641104
650 4 $a Philosophy. $3 516511
690 $a 0493
690 $a 0306
690 $a 0287
690 $a 0487
690 $a 0202
690 $a 0379
690 $a 0485
690 $a 0537
690 $a 0369
690 $a 0351
690 $a 0982
690 $a 0564
690 $a 0422
710 2 $a The University of Liverpool (United Kingdom). $3 1684840
773 0 $t Dissertations Abstracts International $g 83-06B.
790 $a 0722
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28871421