Marrow Adipocyte Senescence in the Pathogenesis of Bone Loss

de Paula FJA, Rosen CJ. Marrow Adipocytes: Origin, Structure, and Function. Annu Rev Physiol. 2020;82:461–84.

Article  PubMed  Google Scholar 

Khosla S, Farr JN, Tchkonia T, Kirkland JL. The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020;16(5):263–75.

Article  CAS  PubMed  Google Scholar 

Farr JN, Khosla S. Cellular senescence in bone. Bone. 2019;121:121–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farr JN, Kaur J, Doolittle ML, Khosla S. Osteocyte Cellular Senescence. Curr Osteoporos Rep. 2020;18(5):559–67.

Article  PubMed  PubMed Central  Google Scholar 

Khosla S, Farr JN, Monroe DG. Cellular senescence and the skeleton: pathophysiology and therapeutic implications. J Clin Invest. 2022;132(3):e154888.

Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.

Article  CAS  PubMed  Google Scholar 

Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D, Barrett JC. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A. 1996;93(24):13742–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003;22(16):4212–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chandra A, Lagnado AB, Farr JN, Monroe DG, Park S, Hachfeld C, Tchkonia T, Kirkland JL, Khosla S, Passos JF, Pignolo RJ. Targeted Reduction of Senescent Cell Burden Alleviates Focal Radiotherapy-Related Bone Loss. J Bone Miner Res. 2020;35(6):1119–31.

Article  CAS  PubMed  Google Scholar 

Chandra A, Lagnado AB, Farr JN, Schleusner M, Monroe DG, Saul D, Passos JF, Khosla S, Pignolo RJ. Bone Marrow Adiposity in Models of Radiation- and Aging-Related Bone Loss Is Dependent on Cellular Senescence. J Bone Miner Res. 2022;37(5):997–1011.

Article  CAS  PubMed  Google Scholar 

Chandra A, Lagnado AB, Farr JN, Doolittle M, Tchkonia T, Kirkland JL, LeBrasseur NK, Robbins PD, Niedernhofer LJ, Ikeno Y, Passos JF, Monroe DG, Pignolo RJ, Khosla S. Targeted clearance of p21- but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity. Aging Cell. 2022;21(5): e13602.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yao Z, Murali B, Ren Q, Luo X, Faget DV, Cole T, Ricci B, Thotala D, Monahan J, van Deursen JM, Baker D, Faccio R, Schwarz JK, Stewart SA. Therapy-Induced Senescence Drives Bone Loss. Cancer Res. 2020;80(5):1171–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu X, Gu Y, Kumar S, Amin S, Guo Q, Wang J, Fang CL, Cao X, Wan M. Oxylipin-PPARgamma-initiated adipocyte senescence propagates secondary senescence in the bone marrow. Cell Metab. 2023;35(4):667-684.e6. This was the first study to establish that glucocorticoid therapy causes the premature accumulation of senescent bone marrow adipocytes in mice.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ogrodnik M, Miwa S, Tchkonia T, Tiniakos D, Wilson CL, Lahat A, Day CP, Burt A, Palmer A, Anstee QM, Grellscheid SN, Hoeijmakers JHJ, Barnhoorn S, Mann DA, Bird TG, Vermeij WP, Kirkland JL, Passos JF, von Zglinicki T, Jurk D. Cellular senescence drives age-dependent hepatic steatosis. Nat Commun. 2017;8:15691.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, Prata LG, van Dijk TH, Verkade E, Casaclang-Verzosa G, Johnson KO, Cubro H, Doornebal EJ, Ogrodnik M, Jurk D, Jensen MD, Chini EN, Miller JD, Matveyenko A, Stout MB, Schafer MJ, White TA, Hickson LJ, Demaria M, Garovic V, Grande J, Arriaga EA, Kuipers F, von Zglinicki T, LeBrasseur NK, Campisi J, Tchkonia T, Kirkland JL. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. 2019;18(3): e12950.

Article  PubMed  PubMed Central  Google Scholar 

Ogrodnik M, Zhu Y, Langhi LGP, Tchkonia T, Kruger P, Fielder E, Victorelli S, Ruswhandi RA, Giorgadze N, Pirtskhalava T, Podgorni O, Enikolopov G, Johnson KO, Xu M, Inman C, Palmer AK, Schafer M, Weigl M, Ikeno Y, Burns TC, Passos JF, von Zglinicki T, Kirkland JL, Jurk D. Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis. Cell Metab. 2019;29(5):1061-1077.e8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thompson PJ, Shah A, Ntranos V, Van Gool F, Atkinson M, Bhushan A. Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes. Cell Metab. 2019;29(5):1045-1060.e10.

Article  CAS  PubMed  Google Scholar 

Aguayo-Mazzucato C, Andle J, Lee TB Jr, Midha A, Talemal L, Chipashvili V, Hollister-Lock J, van Deursen J, Weir G, Bonner-Weir S. Acceleration of beta Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes. Cell Metab. 2019;30(1):129-142.e4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eckhardt BA, Rowsey JL, Thicke BS, Fraser DG, O'Grady KL, Bondar OP, et al. Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes. JCI Insight. 2020;5(9):e135236.

Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, Gil J, Hara E, Krizhanovsky V, Jurk D, Maier AB, Narita M, Niedernhofer L, Passos JF, Robbins PD, Schmitt CA, Sedivy J, Vougas K, von Zglinicki T, Zhou D, Serrano M, Demaria M. Cellular Senescence: Defining a Path Forward. Cell. 2019;179(4):813–27.

Article  CAS  PubMed  Google Scholar 

Swanson EC, Manning B, Zhang H, Lawrence JB. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J Cell Biol. 2013;203(6):929–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hewitt G, Jurk D, Marques FD, Correia-Melo C, Hardy T, Gackowska A, Anderson R, Taschuk M, Mann J, Passos JF. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat Commun. 2012;3:708.

Article  PubMed  Google Scholar 

Doolittle ML, Saul D, Kaur J, Rowsey JL, Vos SJ, Pavelko KD, Farr JN, Monroe DG, Khosla S. Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton. Nat Commun. 2023;14(1):4587.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 2019;38(5):e100492.

Zhang X, Habiballa L, Aversa Z, Ng YE, Sakamoto AE, Englund DA, Pearsall VM, White TA, Robinson MM, Rivas DA, Dasari S, Hruby AJ, Lagnado AB, Jachim SK, Granic A, Sayer AA, Jurk D, Lanza IR, Khosla S, Fielding RA, Nair KS, Schafer MJ, Passos JF, LeBrasseur NK. Characterization of cellular senescence in aging skeletal muscle. Nat Aging. 2022;2(7):601–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farr JN, Fraser DG, Wang H, Jaehn K, Ogrodnik MB, Weivoda MM, Drake MT, Tchkonia T, LeBrasseur NK, Kirkland JL, Bonewald LF, Pignolo RJ, Monroe DG, Khosla S. Identification of Senescent Cells in the Bone Microenvironment. J Bone Miner Res. 2016;31(11):1920–9.

Article  CAS  PubMed  Google Scholar 

Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, Inman CL, Ogrodnik MB, Hachfeld CM, Fraser DG, Onken JL, Johnson KO, Verzosa GC, Langhi LGP, Weigl M, Giorgadze N, LeBrasseur NK, Miller JD, Jurk D, Singh RJ, Allison DB, Ejima K, Hubbard GB, Ikeno Y, Cubro H, Garovic VD, Hou X, Weroha SJ, Robbins PD, Niedernhofer LJ, Khosla S, Tchkonia T, Kirkland JL. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009;15(9):1082–7.

Article  CAS  PubMed  Google Scholar 

Espinosa De Ycaza AE, Sondergaard E, Morgan-Bathke M, Carranza Leon BG, Lytle KA, Ramos P, Kirkland JL, Tchkonia T, Jensen MD. Senescent cells in human adipose tissue: A cross-sectional study. Obesity (Silver Spring). 2021;29(8):1320–7.

Article  CAS  PubMed  Google Scholar 

Palmer AK, Tchkonia T, LeBrasseur NK, Chini EN, Xu M, Kirkland JL. Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity. Diabetes. 2015;64(7):2289–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Palmer AK, Gustafson B, Kirkland JL, Smith U. Cellular senescence: at the nexus between ageing and diabetes. Diabetologia. 2019;62(10):1835–41.

Article  PubMed  PubMed Central  Google Scholar 

Palmer AK, Tchkonia T, Kirkland JL. Senolytics: potential for alleviating diabetes and its complications. Endocrinol. 2021;162(8):bqab058.

Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL. Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife. 2015;4: e12997.

Article  PubMed  PubMed Central  Google Scholar 

Gustafson B, Nerstedt A, Smith U. Reduced subcutaneous adipogenesis in human hypertrophic obesity is linked to senescent precursor cells. Nat Commun. 2019;10(1):2757.

Article  PubMed  PubMed Central  Google Scholar 

Schwartz AV, Sigurdsson S, Hue TF, Lang TF, Harris TB, Rosen CJ, Vittinghoff E, Siggeirsdottir K, Sigurdsson G, Oskarsdottir D, Shet K, Palermo L, Gudnason V, Li X. Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab. 2013;98(6):2294–300.

留言 (0)

沒有登入
gif