Skeletal Phenotypes and Molecular Mechanisms in Aging Mice

Overview

Journal Zool Res

Publisher Science Press

Specialties Biology
Veterinary Medicine

Date 2024 Jun 19

PMID 38894518

Authors

Qiao Guan

Yuan Zhang

Zhi-Kun Wang

Xiao-Hua Liu

Jun Zou

Ling-Li Zhang

Affiliations

Soon will be listed here.

Abstract

Aging is an inevitable physiological process, often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks. Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations, difficulties in sampling, regional variability, and substantial investment. Consequently, mice are preferred for such studies due to their similar motor system structure and function to humans, ease of handling and care, low cost, and short generation time. In this review, we present a comprehensive overview of the characteristics, limitations, applicability, bone phenotypes, and treatment methods in naturally aging mice and prematurely aging mouse models (including , mutant, , , , , , , and -deficient mice). We also summarize the molecular mechanisms of these aging mouse models, including cellular DNA damage response, senescence-related secretory phenotype, telomere shortening, oxidative stress, bone marrow mesenchymal stem cell (BMSC) abnormalities, and mitochondrial dysfunction. Overall, this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases.

References

Lei Y, Martinez C, Torres-Odio S, Bell S, Birdwell C, Bryant J . Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice. Sci Adv. 2021; 7(22). PMC: 8153723. DOI: 10.1126/sciadv.abe7548. View

Wang J, Clauson C, Robbins P, Niedernhofer L, Wang Y . The oxidative DNA lesions 8,5'-cyclopurines accumulate with aging in a tissue-specific manner. Aging Cell. 2012; 11(4):714-6. PMC: 3399950. DOI: 10.1111/j.1474-9726.2012.00828.x. View

Almeida M, Ambrogini E, Han L, Manolagas S, Jilka R . Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic Wnt signaling in the skeleton. J Biol Chem. 2009; 284(40):27438-48. PMC: 2785673. DOI: 10.1074/jbc.M109.023572. View

Gregg S, Robinson A, Niedernhofer L . Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA Repair (Amst). 2011; 10(7):781-91. PMC: 3139823. DOI: 10.1016/j.dnarep.2011.04.026. View

Levin V, Jiang X, Kagan R . Estrogen therapy for osteoporosis in the modern era. Osteoporos Int. 2018; 29(5):1049-1055. DOI: 10.1007/s00198-018-4414-z. View

Carreira M, Izquierdo A, Amil M, Casanueva F, Crujeiras A . Oxidative Stress Induced by Excess of Adiposity Is Related to a Downregulation of Hepatic SIRT6 Expression in Obese Individuals. Oxid Med Cell Longev. 2019; 2018:6256052. PMC: 6317113. DOI: 10.1155/2018/6256052. View

Dairaghi D, Shadel G, Clayton D . Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box-containing protein into a transcriptional activator. J Mol Biol. 1995; 249(1):11-28. DOI: 10.1006/jmbi.1995.9889. View

Segre D, SEGRE M . Age-related changes in B and T lymphocytes and decline of humoral immune responsiveness in aged mice. Mech Ageing Dev. 1977; 6(2):115-29. DOI: 10.1016/0047-6374(77)90013-6. View

Farr J, Fraser D, Wang H, Jaehn K, Ogrodnik M, Weivoda M . Identification of Senescent Cells in the Bone Microenvironment. J Bone Miner Res. 2016; 31(11):1920-1929. PMC: 5289710. DOI: 10.1002/jbmr.2892. View

10.

Lee J, Ward W, Ren H, Vallanat B, Darlington G, Han E . Meta-analysis of gene expression in the mouse liver reveals biomarkers associated with inflammation increased early during aging. Mech Ageing Dev. 2012; 133(7):467-78. DOI: 10.1016/j.mad.2012.05.006. View

11.

Moerman E, Teng K, Lipschitz D, Lecka-Czernik B . Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004; 3(6):379-89. PMC: 1850101. DOI: 10.1111/j.1474-9728.2004.00127.x. View

12.

Manandhar M, Boulware K, Wood R . The ERCC1 and ERCC4 (XPF) genes and gene products. Gene. 2015; 569(2):153-61. PMC: 4536074. DOI: 10.1016/j.gene.2015.06.026. View

13.

Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A . Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment. Int J Mol Sci. 2018; 19(2). PMC: 5855582. DOI: 10.3390/ijms19020360. View

14.

Olivieri F, Albertini M, Orciani M, Ceka A, Cricca M, Procopio A . DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging. Oncotarget. 2015; 6(34):35509-21. PMC: 4742121. DOI: 10.18632/oncotarget.5899. View

15.

Kipling D, Faragher R . Progeroid syndromes: probing the molecular basis of aging?. Mol Pathol. 1998; 50(5):234-41. PMC: 379638. DOI: 10.1136/mp.50.5.234. View

16.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

17.

Chen X, Li L, Guo J, Zhang L, Yuan Y, Chen B . Treadmill running exercise prevents senile osteoporosis and upregulates the Wnt signaling pathway in SAMP6 mice. Oncotarget. 2016; 7(44):71072-71086. PMC: 5342064. DOI: 10.18632/oncotarget.12125. View

18.

Liang K, Kristiansen C, Mostafavi S, Vatne G, Zantingh G, Kianian A . Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations. EMBO Mol Med. 2020; 12(10):e12146. PMC: 7539330. DOI: 10.15252/emmm.202012146. View

19.

Niedernhofer L, Gurkar A, Wang Y, Vijg J, Hoeijmakers J, Robbins P . Nuclear Genomic Instability and Aging. Annu Rev Biochem. 2018; 87:295-322. DOI: 10.1146/annurev-biochem-062917-012239. View

20.

Radulescu C, Cerar V, Haslehurst P, Kopanitsa M, Barnes S . The aging mouse brain: cognition, connectivity and calcium. Cell Calcium. 2021; 94:102358. DOI: 10.1016/j.ceca.2021.102358. View