Determining the feasibility of characterising cellular senescence in human skeletal muscle and exploring associations with muscle morphology and physical function at different ages: findings from the MASS_Lifecourse Study.
Cellular senescence
Human skeletal muscle ageing
Muscle morphology
Physical function
Sarcopenia
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
11 Jul 2023
11 Jul 2023
Historique:
received:
13
04
2023
accepted:
05
07
2023
medline:
12
7
2023
pubmed:
12
7
2023
entrez:
11
7
2023
Statut:
aheadofprint
Résumé
Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47-84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = - 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = - 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.
Identifiants
pubmed: 37434081
doi: 10.1007/s11357-023-00869-4
pii: 10.1007/s11357-023-00869-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R01 AG068048
Pays : United States
Organisme : NCI NIH HHS
ID : UG3 CA268103
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183–95.
pubmed: 25294644
doi: 10.1007/s00223-014-9915-y
Wilkinson DJ, Piasecki M, Atherton PJ. The age-related loss of skeletal muscle mass and function: measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans. Ageing Res Rev. 2018;47:123–32.
pubmed: 30048806
pmcid: 6202460
doi: 10.1016/j.arr.2018.07.005
McLeod M, Breen L, Hamilton DL, Philp A. Live strong and prosper: the importance of skeletal muscle strength for healthy ageing. Biogerontology. 2016;17:497–510.
pubmed: 26791164
pmcid: 4889643
doi: 10.1007/s10522-015-9631-7
Li R, Xia J, Zhang XI, Gathirua-Mwangi WG, Guo J, Li Y, et al. Associations of muscle mass and strength with all-cause mortality among US older adults. Med Sci Sports Exerc. 2018;50:458–67.
pubmed: 28991040
pmcid: 5820209
doi: 10.1249/MSS.0000000000001448
Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019;393:2636–46.
pubmed: 31171417
doi: 10.1016/S0140-6736(19)31138-9
Tsekoura M, Kastrinis A, Katsoulaki M, Billis E, Gliatis J. Sarcopenia and its impact on quality of life. Adv Exp Med Biol. 2017;987:213–8.
pubmed: 28971460
doi: 10.1007/978-3-319-57379-3_19
Pinedo-Villanueva R, Westbury LD, Syddall HE, Sanchez-Santos MT, Dennison EM, Robinson SM, et al. Health care costs associated with muscle weakness: a UK population-based estimate. Calcif Tissue Int. 2019;104:137–44.
pubmed: 30244338
doi: 10.1007/s00223-018-0478-1
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019; 48:16–31. Erratum in: Age Ageing. 2019;48:601
Sayer AA, Cruz-Jentoft A. Sarcopenia definition, diagnosis and treatment: consensus is growing. Age Ageing. 2022;51(10):afac220.
pubmed: 36273495
pmcid: 9588427
doi: 10.1093/ageing/afac220
Hurst C, Robinson SM, Witham MD, Dodds RM, Granic A, Buckland C, et al. Resistance exercise as a treatment for sarcopenia: prescription and delivery. Age Ageing. 2022;51:afac003.
pubmed: 35150587
pmcid: 8840798
doi: 10.1093/ageing/afac003
Dodds RM, Hurst C, Hillman SJ, Davies K, Roberts L, Aspray TJ, et al. Advancing our understanding of skeletal muscle across the lifecourse: Protocol for the MASS_Lifecourse study and characteristics of the first 80 participants. Exp Gerontol. 2022;166:111884.
pubmed: 35788023
doi: 10.1016/j.exger.2022.111884
Dodds R, Aihie Sayer A. A lifecourse approach to sarcopenia. In: Cruz-Jentoft AJ, Morley JE, editors. Sarcopenia. Wiley Blackwell; 2021;77–93.
Callahan CM, Foroud T, Saykin AJ, Shekhar A, Hendrie HC. Translational research on aging: clinical epidemiology as a bridge between the sciences. Transl Res. 2014;163:439–45.
pubmed: 24090769
doi: 10.1016/j.trsl.2013.09.002
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2022;S0092–8674(22):01377.
Kowald A, Passos JF, Kirkwood TBL. On the evolution of cellular senescence. Aging Cell. 2020;19:e13270.
pubmed: 33166065
pmcid: 7744960
doi: 10.1111/acel.13270
Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell. 2019;179:813–27.
pubmed: 31675495
doi: 10.1016/j.cell.2019.10.005
Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28:436–53.
pubmed: 29477613
doi: 10.1016/j.tcb.2018.02.001
Lopes-Paciencia S, Saint-Germain E, Rowell MC, Ruiz AF, Kalegari P, Ferbeyre G. The senescence-associated secretory phenotype and its regulation. Cytokine. 2019;117:15–22.
pubmed: 30776684
doi: 10.1016/j.cyto.2019.01.013
Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15:978–90.
pubmed: 23770676
pmcid: 3732483
doi: 10.1038/ncb2784
Tuttle CSL, Luesken SWM, Waaijer MEC, Maier AB. Senescence in tissue samples of humans with age-related diseases: a systematic review. Ageing Res Rev. 2021;68:101334.
pubmed: 33819674
doi: 10.1016/j.arr.2021.101334
van Deursen JM. The role of senescent cells in ageing. Nature. 2014;509:439–46.
pubmed: 24848057
pmcid: 4214092
doi: 10.1038/nature13193
Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, et al. Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov. 2017;16:718–35.
pubmed: 28729727
pmcid: 5942225
doi: 10.1038/nrd.2017.116
Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24:1246–56.
pubmed: 29988130
pmcid: 6082705
doi: 10.1038/s41591-018-0092-9
Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232–6.
pubmed: 22048312
pmcid: 3468323
doi: 10.1038/nature10600
Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence. Nat Rev Cancer. 2015;15:397–408. Erratum in: Nat Rev Cancer.2015;15:509.
Edwards MG, Anderson RM, Yuan M, Kendziorski CM, Weindruch R, Prolla TA. Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. BMC Genomics. 2007;8:80.
pubmed: 17381838
pmcid: 1847444
doi: 10.1186/1471-2164-8-80
Welle S, Brooks AI, Delehanty JM, Needler N, Bhatt K, Shah B, et al. Skeletal muscle gene expression profiles in 20–29 year old and 65–71 year old women. Exp Gerontol. 2004;39:369–77.
pubmed: 15036396
doi: 10.1016/j.exger.2003.11.011
Coppé JP, Rodier F, Patil CK, Freund A, Desprez PY, Campisi J. Tumor suppressor and aging biomarker p16(INK4a) induces cellular senescence without the associated inflammatory secretory phenotype. J Biol Chem. 2011;286:36396–403.
pubmed: 21880712
pmcid: 3196093
doi: 10.1074/jbc.M111.257071
He Y, Xie W, Li H, Jin H, Zhang Y, Li Y. Cellular senescence in sarcopenia: possible mechanisms and therapeutic potential. Front Cell Dev Biol. 2022;9:793088.
pubmed: 35083219
pmcid: 8784872
doi: 10.3389/fcell.2021.793088
Zhang X, Habiballa L, Aversa Z, Ng YE, Sakamoto AE, Englund DA, et al. Characterization of cellular senescence in aging skeletal muscle. Nat Aging. 2022;2:601–15.
pubmed: 36147777
pmcid: 9491365
doi: 10.1038/s43587-022-00250-8
Dungan CM, Peck BD, Walton RG, Huang Z, Bamman MM, Kern PA, et al. In vivo analysis of γH2A.X+ cells in skeletal muscle from aged and obese humans. FASEB J. 2020;34:7018–35.
pubmed: 32246795
doi: 10.1096/fj.202000111RR
Mecocci P, Fanó G, Fulle S, MacGarvey U, Shinobu L, Polidori MC, et al. Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle. Free Radic Biol Med. 1999;26:303–8.
pubmed: 9895220
doi: 10.1016/S0891-5849(98)00208-1
Kao TW, Chen WL, Han DS, Huang YH, Chen CL, Yang WS. Examining how p16(INK4a) expression levels are linked to handgrip strength in the elderly. Sci Rep. 2016;6:31905.
pubmed: 27549351
pmcid: 4994020
doi: 10.1038/srep31905
Lawrence I, Bene M, Nacarelli T, Azar A, Cohen JZ, Torres C, et al. Correlations between age, functional status, and the senescence-associated proteins HMGB2 and p16
pubmed: 29651745
pmcid: 5964056
doi: 10.1007/s11357-018-0015-1
Fielding RA, Atkinson EJ, Aversa Z, White TA, Heeren AA, Achenbach SJ, et al. Associations between biomarkers of cellular senescence and physical function in humans: observations from the lifestyle interventions for elders (LIFE) study. Geroscience. 2022;44:2757–70.
pubmed: 36367600
pmcid: 9768064
doi: 10.1007/s11357-022-00685-2
Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One. 2014;9:e113637.
pubmed: 25474696
pmcid: 4256164
doi: 10.1371/journal.pone.0113637
Office of National Statistics. ONS Occupation Coding Tool. 2021; Available at: https: //onsdigital.github.io/dp-classification-tools/standard-occupational-classification /ONS_SOC_occupation_coding_tool.html.
Malmstrom TK, Morley JE. SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. J Am Med Dir Assoc. 2013;14:531–2.
pubmed: 23810110
doi: 10.1016/j.jamda.2013.05.018
Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40:423–9.
pubmed: 21624928
doi: 10.1093/ageing/afr051
Dodds RM, Murray JC, Granic A, Hurst C, Uwimpuhwe G, Richardson S, et al. Prevalence and factors associated with poor performance in the 5-chair stand test: findings from the Cognitive Function and Ageing Study II and proposed Newcastle protocol for use in the assessment of sarcopenia. J Cachexia Sarcopenia Muscle. 2021;12:308–18.
pubmed: 33463015
pmcid: 8061374
doi: 10.1002/jcsm.12660
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82.
pubmed: 22743772
doi: 10.1038/nmeth.2019
Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ: Erlbaum; 1988.
Lexell J, Taylor CC, Sjöström M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci. 1988;84:275–94.
pubmed: 3379447
doi: 10.1016/0022-510X(88)90132-3
Larsson L, Sjödin B, Karlsson J. Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22–65 years. Acta Physiol Scand. 1978;103:31–9.
pubmed: 208350
doi: 10.1111/j.1748-1716.1978.tb06187.x
Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Exp Gerontol. 2013;48:492–8.
pubmed: 23425621
doi: 10.1016/j.exger.2013.02.012
Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020;288:518–36.
pubmed: 32686219
pmcid: 7405395
doi: 10.1111/joim.13141
Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMed. 2019;40:554–63.
doi: 10.1016/j.ebiom.2018.12.052
Martyanov V, Whitfield ML, Varga J. Senescence signature in skin biopsies from systemic sclerosis patients treated with senolytic therapy: potential predictor of clinical response? Arthritis Rheumatol. 2019;71:1766–7.
pubmed: 31112009
pmcid: 7863581
doi: 10.1002/art.40934
Sharma AK, Roberts RL, Benson RD Jr, Pierce JL, Yu K, Hamrick MW, et al. The senolytic drug navitoclax (ABT-263) causes trabecular bone loss and impaired osteoprogenitor function in aged mice. Front Cell Dev Biol. 2020;8:354.
pubmed: 32509782
pmcid: 7252306
doi: 10.3389/fcell.2020.00354
Raffaele M, Vinciguerra M. The costs and benefits of senotherapeutics for human health. Lancet Healthy Longev. 2022;3(1):e67–77.
pubmed: 36098323
doi: 10.1016/S2666-7568(21)00300-7
Börsch A, Ham DJ, Mittal N, Tintignac LA, Migliavacca E, Feige JN, et al. Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia. Commun Biol. 2021;4:194.
pubmed: 33580198
pmcid: 7881157
doi: 10.1038/s42003-021-01723-z
Terry EE, Zhang X, Hoffmann C, Hughes LD, Lewis SA, Li J, et al. Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues. Elife. 2018;7:e34613.
pubmed: 29809149
pmcid: 6008051
doi: 10.7554/eLife.34613
Picard M, Hepple RT, Burelle Y. Mitochondrial functional specialization in glycolytic and oxidative muscle fibers: tailoring the organelle for optimal function. Am J Physiol Cell Physiol. 2012;302:C629–41.
pubmed: 22031602
doi: 10.1152/ajpcell.00368.2011
Rubenstein AB, Smith GR, Raue U, Begue G, Minchev K, Ruf-Zamojski F, et al. Single-cell transcriptional profiles in human skeletal muscle. Sci Rep. 2020;10:229.
pubmed: 31937892
pmcid: 6959232
doi: 10.1038/s41598-019-57110-6
Saul D, Kosinsky RL, Atkinson EJ, Doolittle ML, Zhang X, LeBrasseur NK, et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat Commun. 2022;13:4827.
pubmed: 35974106
pmcid: 9381717
doi: 10.1038/s41467-022-32552-1
Englund DA, Jolliffe A, Aversa Z, Zhang X, Sturmlechner I, Sakamoto AE, et al. p21 induces a senescence program and skeletal muscle dysfunction. Mol Metab. 2023;67:101652.
pubmed: 36509362
doi: 10.1016/j.molmet.2022.101652
Strandkvist V, Larsson A, Pauelsen M, Nyberg L, Vikman I, Lindberg A, et al. Hand grip strength is strongly associated with lower limb strength but only weakly with postural control in community-dwelling older adults. Arch Gerontol Geriatr. 2021;94:104345.
pubmed: 33497911
doi: 10.1016/j.archger.2021.104345
Sayer AA, Kirkwood TB. Grip strength and mortality: a biomarker of ageing? Lancet. 2015;386(9990):226–7.
pubmed: 25982159
doi: 10.1016/S0140-6736(14)62349-7