New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary
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Genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, deregulated nutrient-sensing, cellular senescence, stem cell exhaustion, and altered intercellular communication were the original nine hallmarks of ageing proposed by López-Otín and colleagues in 2013. The proposal of these hallmarks of ageing has been instrumental in guiding and pushing forward research on the biology of ageing. In the nearly past 10 years, our in-depth exploration on ageing research has enabled us to formulate new hallmarks of ageing which are compromised autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, and inflammation, among other emerging ones. Amalgamation of the 'old' and 'new' hallmarks of ageing may provide a more comprehensive explanation of ageing and age-related diseases, shedding light on interventional and therapeutic studies to achieve healthy, happy, and productive lives in the elderly.
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Maintenance of organizational spatial compartmentalization is a hallmark of organismal health, while aging is associated with a decline in this capacity.
“Maintenance of organizational spatial compartmentalization is a hallmark of organismal health, while aging is associated with a decline in this capacity.56”
From Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging (2024) · cites this paper as [56]
In the Introduction (Box 1; page not available), the paper says the nuclear lamina becomes destabilised during ageing, allowing chromatin to enter the cytoplasm. This supports a specific age-related loss of cellular compartmentalisation, but the paper does not identify maintenance of spatial compartmentalisation broadly as a hallmark of organismal health. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe accumulation of senescent cells contributes to tissue and organismal aging and is a well-known aging hallmark.
“The accumulation of senescent cells contributes to tissue and organismal aging and is a well-known aging hallmark.56”
From Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging (2024) · cites this paper as [56]
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Pleiotropy, natural selection, and the evolution of senescence.
Williams, G. C. (1957) · Evolution · doi:10.1111/j.1558-5646.1957.tb02911.x · Cited by 4,279 · cited 1× · see citing works
“Secondly, he highlighted the antagonistic pleiotropy hypothesis [30], which outlines that genes leading to harmful effects in old age might not be selected against due to an advantage in early life.”
BackgroundRapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · cited 1× · see citing works
“Finally, mTOR inhibition also alleviated markers of genomic instability and telomere attrition in senescent cells, demonstrating the value of mTOR inhibitors as geroprotectors, consistent with numerous findings from preclinical model organisms [36]; new studies in dogs (DogAgeing Project) and Humans (PEARL Trial) will…”
BackgroundInflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Inflammaging: a new immune–metabolic viewpoint for age-related diseases
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0059-4 · Cited by 3,586 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · see citing works
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045 · see citing works
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617 · see citing works
Self-citationBaar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454 · see citing works
The coming of age of chaperone-mediated autophagy
Kaushik, S., & Cuervo, A. M. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0001-6 · Cited by 1,422 · see citing works
Autophagy in healthy aging and disease
Aman, Y., Schmauck-Medina, T., Hansen, M., Morimoto, R. I., Simon, A. K., Bjedov, I., Palikaras, K., Simonsen, A., Johansen, T., Tavernarakis, N., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00098-4 · Cited by 1,313 · see citing works
Self-citationSenolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2018.12.052 · Cited by 1,261 · see citing works
NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061 · see citing works
Kirkwood, T. B. L. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00419-5 · Cited by 801 · cited 1× · see citing works
“The theory of the disposable soma [29] describes that an organism has limited resources, which it has to allocate strategically.”
BackgroundSelf-citationNAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790 · see citing works
Self-citationDefective Mitophagy in XPA via PARP-1 Hyperactivation and NAD+/SIRT1 Reduction
Fang, E. F., Scheibye-Knudsen, M., Brace, L. E., Kassahun, H., SenGupta, T., Nilsen, H., Mitchell, J. R., Croteau, D. L., & Bohr, V. A. (2014) · Cell · doi:10.1016/j.cell.2014.03.026 · Cited by 711 · see citing works
Self-citationGut microbiome pattern reflects healthy ageing and predicts survival in humans
Wilmanski, T. M., Diener, C., Rappaport, N., Patwardhan, S., Wiedrick, J. T., Lapidus, J., Earls, J. C., Zimmer, A., Glusman, G., Robinson, M., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00348-0 · Cited by 693 · see citing works
Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice
Fernández, Á. F., Sebti, S., Wei, Y., Zou, Z., Shi, M., McMillan, K. L., He, C., Ting, T., Liu, Y., Chiang, W.-C., et al. (2018) · Nature · doi:10.1038/s41586-018-0162-7 · Cited by 630 · see citing works
Lou, G., Palikaras, K., Lautrup, S., Scheibye‐Knudsen, M., Tavernarakis, N., & Fang, E. F. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.07.002 · Cited by 449 · see citing works
Self-citationSenescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages
Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00305-3 · Cited by 420 · see citing works
Self-citationCapell, B. C., Erdos, M. R., Madigan, J. P., Fiordalisi, J. J., Varga, R., Conneely, K. N., Gordon, L. B., Der, C. J., Cox, A. D., & Collins, F. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506001102 · Cited by 395 · see citing works
Mitophagy in neurodegeneration and aging
Fivenson, E. M., Lautrup, S., Sun, N., Scheibye-Knudsen, M., Stevnsner, T., Nilsen, H., Bohr, V. A., & Fang, E. F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.007 · Cited by 364 · see citing works
Self-citationVizioli, M. G., Liu, T., Miller, K. N., Robertson, N. A., Gilroy, K., Lagnado, A. B., Perez-Garcia, A., Kiourtis, C., Dasgupta, N., Lei, X., et al. (2020) · Genes & Development · doi:10.1101/gad.331272.119 · Cited by 359 · see citing works
Xie, C., Zhuang, X., Niu, Z., Ai, R., Lautrup, S., Zheng, S., Jiang, Y., Han, R., Gupta, T. S., Cao, S., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00819-5 · Cited by 347 · see citing works
Self-citationProtecting the mitochondrial powerhouse
Scheibye‐Knudsen, M., Fang, E. F., Croteau, D. L., Wilson, D. M., & Bohr, V. A. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.11.002 · Cited by 330 · see citing works
Self-citationTargeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis
Fouquerel, E., Barnes, R. P., Uttam, S., Watkins, S. C., Bruchez, M. P., & Opresko, P. L. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.04.024 · Cited by 275 · see citing works
Self-citationSpatial confinement downsizes the inflammatory response of macrophages
Jain, N., & Vogel, V. (2018) · Nature Materials · doi:10.1038/s41563-018-0190-6 · Cited by 271 · see citing works
Ageing: from inflammation to cancer
Leonardi, G. C., Accardi, G., Monastero, R., Nicoletti, F., & Libra, M. (2018) · Immunity & Ageing · doi:10.1186/s12979-017-0112-5 · Cited by 241 · see citing works
Gordon, L. B., Shappell, H. M., Massaro, J., D’Agostino, R. B., Brazier, J. F., Campbell, S. E., Kleinman, M. E., & Kieran, M. W. (2018) · JAMA · doi:10.1001/jama.2018.3264 · Cited by 223 · see citing works
Autophagy in aging and longevity
Wong, S. Q., Kumar, A. V., Mills, J., & Lapierre, L. R. (2019) · Human Genetics · doi:10.1007/s00439-019-02031-7 · Cited by 204 · see citing works
The cross talk between microbiota and the immune system: metabolites take center stage
Shapiro, H., Thaiss, C. A., Levy, M., & Elinav, E. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.07.003 · Cited by 189 · see citing works
Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function
Mansell, E., Sigurðsson, V., Deltcheva, E. M., Brown, J., James, C. T., Miharada, K., Soneji, S., Larsson, J. T., & Enver, T. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.09.018 · Cited by 176 · see citing works
Self-citationTelomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening
Barnes, R. P., Rosa, M. D., Thosar, S. A., Detwiler, A. C., Roginskaya, V. Y., Houten, B. V., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00790-y · Cited by 136 · see citing works
Self-citationThe hoverfly and the wasp: A critique of the hallmarks of aging as a paradigm
Gems, D., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101407 · Cited by 134 · see citing works
Diabetes mellitus correlates with increased biological age as indicated by clinical biomarkers
Bahour, N., Cortez, B., Pan, H., Shah, H., Doria, A., & Aguayo-Mazzucato, C. (2022) · GeroScience · doi:10.1007/s11357-021-00469-0 · Cited by 121 · see citing works
Alsaleh, G., Panse, I., Swadling, L., Zhang, H., Richter, F. C., Meyer, A., Lord, J., Barnes, E., Klenerman, P., Green, C., et al. (2020) · eLife · doi:10.7554/elife.57950 · Cited by 120 · see citing works
Reversal of phenotypes of cellular senescence by pan-mTOR inhibition
Walters, H. E., Deneka-Hannemann, S., & Cox, L. S. (2016) · Aging · doi:10.18632/aging.100872 · Cited by 113 · see citing works
Self-citationChanges in splicing factor expression are associated with advancing age in man
Holly, A. C., Melzer, D. R., Pilling, L. C., Fellows, A. D., Tanaka, T., Ferrucci, L., & Harries, L. W. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.05.006 · Cited by 111 · see citing works
Sapey, E., Patel, J. M., Greenwood, H. L., Walton, G., Grudzinska, F. S., Parekh, D., Mahida, R. Y., Dancer, R. C. A., Lugg, S. T., Howells, P., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201812-2328oc · Cited by 96 · see citing works
Latorre, E., Birar, V. C., Sheerin, A. N. P., Jeynes, J. C. C., Hooper, A., Dawe, H. R., Melzer, D. R., Cox, L. S., Faragher, R., Ostler, E. L., et al. (2017) · BMC Cell Biology · doi:10.1186/s12860-017-0147-7 · Cited by 94 · see citing works
Self-citationBiological mechanisms of aging predict age‐related disease co‐occurrence in patients
Fraser, H. C., Kuan, V., Johnen, R., Zwierzyna, M., Hingorani, A. D., Beyer, A., & Partridge, L. (2022) · Aging Cell · doi:10.1111/acel.13524 · Cited by 91 · see citing works
Alternative polyadenylation of mRNA and its role in cancer
Yuan, F., Hankey, W., Wagner, E. J., Li, W., & Wang, Q. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.10.011 · Cited by 90 · see citing works
Immunomodulatory Role of Urolithin A on Metabolic Diseases
Toney, A. M., Fox, D., Chaidez, V., Ramer‐Tait, A. E., & Chung, S. (2021) · Biomedicines · doi:10.3390/biomedicines9020192 · Cited by 79 · see citing works
Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome
Okur, M. N., Mao, B., Kimura, R., Haraczy, S. J., Fitzgerald, T. S., Edwards‐Hollingsworth, K., Tian, J. Y., Osmani, W. A., Croteau, D. L., Kelley, M. W., et al. (2020) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-019-0040-z · Cited by 51 · see citing works
Self-citationWalters, H., & Cox, L. S. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6697861 · Cited by 49 · see citing works
Self-citationShen, T., Li, H., Song, Y., Li, L., Lin, J., Wei, G., & Ni, T. (2019) · Aging · doi:10.18632/aging.101836 · Cited by 48 · see citing works
Mohaissen, T., Proniewski, B., Targosz‐Korecka, M., Bar, A., Kij, A., Bułat, K., Wajda, A., Blat, A., Matyjaszczyk‐Gwarda, K., Grosicki, M., et al. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab306 · Cited by 42 · see citing works
Higher physiological vulnerability to hypoxic exposure with advancing age in the human brain
Vestergaard, M. B., Jensen, M. L., Arngrim, N., Lindberg, U., & Larsson, H. B. W. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18818291 · Cited by 38 · see citing works
Self-citationTivey, H. S. E., Brook, A. J. C., Rokicki, M., Kipling, D., & Davis, T. (2012) · Biogerontology · doi:10.1007/s10522-012-9407-2 · Cited by 37 · see citing works
Soendenbroe, C., Dahl, C. L., Meulengracht, C., Tamáš, M., Svensson, R. B., Schjerling, P., Kjaer, M., Andersen, J. L., & Mackey, A. L. (2022) · The Journal of Physiology · doi:10.1113/jp282677 · Cited by 36 · see citing works
Self-citationBar, A., Skórka, T., Jasiński, K., Sternak, M., Bartel, Ż., Tyrankiewicz, U., & Chłopicki, S. (2016) · NMR in Biomedicine · doi:10.1002/nbm.3567 · Cited by 30 · see citing works
Paccosi, E., Costanzo, F., Costantino, M., Balzerano, A., Monteonofrio, L., Soddu, S., Prantera, G., Brancorsini, S., Egly, J., & Proietti‐De‐Santis, L. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006543117 · Cited by 25 · see citing works
Self-citationDefective transcription of ATF3 responsive genes, a marker for Cockayne Syndrome
Epanchintsev, A., Rauschendorf, M., Costanzo, F., Calmels, N., Obringer, C., Sarasin, A. R., Coin, F., Laugel, V., & Egly, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-57999-4 · Cited by 23 · see citing works
Self-citationCao, S., Aman, Y., Fang, E. F., & Tencomnao, T. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02904-5 · Cited by 19 · see citing works
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Kowald, A., & Kirkwood, T. B. L. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111588 · Cited by 18 · see citing works
Self-citationVestergaard, M. B., Lindberg, U., Knudsen, M. H., Urdanibia-Centelles, O., Bakhtiari, A., Mortensen, E. L., Osler, M., Fagerlund, B., Benedek, K., Lauritzen, M., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00596-2 · Cited by 17 · see citing works
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Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
“[415] Schmauck-Medina T, Molière A, Lautrup S, Zhang J, Chlopicki S, Madsen HB,”
Sayer, A. A., Cooper, R., Arai, H., Cawthon, P. M., Essomba, M.-J. N., Fielding, R. A., Grounds, M. D., Witham, M. D., & Cruz-Jentoft, A. J. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00550-w · Cited by 395 · see citing works
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging
Jiménez‐Loygorri, J. I., Villarejo‐Zori, B., Viedma-Poyatos, Á., Zapata‐Muñoz, J., Benítez‐Fernández, R., Frutos-Lisón, M. D., Tomás-Barberán, F. A., Espı́n, J. C., Área-Gómez, E., Gómez-Durán, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45044-1 · Cited by 381 · see citing works
“Major: The authors show that that the age-associated increase in mitophagy is driven by the PINK1/Parkin pathway by looking into the levels of p-Ub (S65).”
InfluentialMa, Z., Zuo, T., Frey, N., & Rangrez, A. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01946-6 · Cited by 297 · see citing works
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement
Tenchov, R., Sasso, J. M., Wang, X., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00531 · Cited by 276 · see citing works
Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis
Arosio, B., Calvani, R., Ferri, E., Coelho-Junior, H. J., Carandina, A., Campanelli, F., Ghiglieri, V., Marzetti, E., & Picca, A. (2023) · Nutrients · doi:10.3390/nu15081853 · Cited by 165 · see citing works
Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
Ma, S., Ji, Z., Zhang, B., Geng, L., Cai, Y., Nie, C., Li, J., Zuo, Y., Sun, Y., Xu, G., et al. (2024) · Cell · doi:10.1016/j.cell.2024.10.019 · Cited by 162 · see citing works
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Song, Q., Zhou, X., Xu, K., Liu, S., Zhu, X., & Yang, J. J. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.08.008 · Cited by 122 · see citing works
Granic, A., Suetterlin, K. J., Shavlakadze, T., Grounds, M. D., & Sayer, A. A. (2023) · Clinical Science · doi:10.1042/cs20230319 · Cited by 115 · see citing works
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Olivieri, F., Biscetti, L., Pimpini, L., Pelliccioni, G., Sabbatinelli, J., & Giunta, S. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102521 · Cited by 110 · see citing works
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“Notably, according to the ITOA, the loss of epigenetic information throughout someone ’ s life is driven by DNA breakage and repair-induced changes and this is a reversible cause of ageing (Lu et al., 2023; Yang et al., 2023).”
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BackgroundLasoń, W., Jantas, D., Leśkiewicz, M., Regulska, M., & Basta‐Kaim, A. (2023) · Cells · doi:10.3390/cells12040660 · Cited by 96 · see citing works
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AMPK: The energy sensor at the crossroads of aging and cancer
Penugurti, V., Manne, R., Bai, L., Kant, R., & Lin, H. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.08.002 · Cited by 83 · see citing works
Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies
Fraile, M., Eiró, N., Costa, L. A., Martín, A., & Vizoso, F. J. (2022) · Biology · doi:10.3390/biology11111678 · Cited by 76 · see citing works
Magnesium and the Hallmarks of Aging
Dominguez, L. J., Veronese, N., & Barbagallo, M. (2024) · Nutrients · doi:10.3390/nu16040496 · Cited by 75 · see citing works
Picca, A., Calvani, R., Coelho‐Júnior, H. J., Marini, F., Landi, F., & Marzetti, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214006 · Cited by 65 · see citing works
“cellular and extracellular mechanical properties, splicing regulation, inflammation) that become impaired during aging [6,7].”
BackgroundGiunta, S., Xia, S., Pelliccioni, G., & Olivieri, F. (2023) · GeroScience · doi:10.1007/s11357-023-00947-7 · Cited by 72 · see citing works
“…“ger-oscience theory,” assuming that aging process is the main culprit of the development of the most common age-related diseases, inflammaging can be defined as a “hallmark of aging” and, at the same time, as the most clinically relevant risk factors for the most common age-related diseases [33].”
BackgroundExtracellular Vesicles in Aging: An Emerging Hallmark?
Manni, G., Buratta, S., Pallotta, M. T., Chiasserini, D., Michele, A. D., Emiliani, C., Giovagnoli, S., Pascucci, L., Romani, R., Bellezza, I., et al. (2023) · Cells · doi:10.3390/cells12040527 · Cited by 63 · see citing works
“These observations led to the inclusion of microbiome dysfunction among the new hallmarks of aging [35].”
BackgroundInfluentialTFEB is a central regulator of the aging process and age-related diseases
Abokyi, S., Ghartey‐Kwansah, G., & Tse, D. Y. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101985 · Cited by 59 · see citing works
“5 altered proteostasis, deregulated nutrient-sensing, DNA damage, and mitochondrial dysfunction (López-Otín et al., 2023; Schmauck-Medina et al., 2022).”
Age-associated inflammation and implications for skeletal muscle responses to exercise
Kunz, H. E., & Lanza, I. R. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112177 · Cited by 56 · see citing works
Calabrò, A., Accardi, G., Aiello, A., Caruso, C., Galimberti, D., & Candore, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031792 · Cited by 54 · see citing works
Lawrence, M., Goyal, A., Pathak, S., & Ganguly, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137411 · Cited by 54 · see citing works
“Cellular senescence can be defined as an irreversible loss of a cell’s proliferative capacity [11] and often results from or into one of the hallmarks of aging including DNA damage, mitochondrial dysfunction and stem cell exhaustion [12,13].”
BackgroundMitochondria break free: Mitochondria-derived vesicles in aging and associated conditions
Ferrucci, L., Guerra, F., Bucci, C., Marzetti, E., & Picca, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102549 · Cited by 52 · see citing works
Metabolic syndrome and epigenetic aging: a twin study
Föhr, T., Hendrix, A., Kankaanpää, A., Laakkonen, E. K., Kujala, U. M., Pietiläinen, K. H., Lehtimäki, T. J., Kähönen, M. A. P., Raitakari, O. T., Wang, X., et al. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01466-x · Cited by 50 · see citing works
“Epigenetics, particularly age-related changes in DNA methylation (DNAm), constitute the primary hallmark of biological aging [10, 11].”
BackgroundMarti-Garcia, D., Martinez-Martinez, A., Sanz, F. J., Devesa-Peiró, A., Sebastián-León, P., del Aguila, N., Pellicer, A., & Díaz-Gimeno, P. (2024) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-024-01323-6 · Cited by 50 · see citing works
“Taken together, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, and microbial dysbiosis–which are all established hallmarks of human aging– reinforce the concept of endometrial aging [19, 159, 160].”
Steering research on mRNA splicing in cancer towards clinical translation
Anczuków, O., Allain, F. H. ‐., Angarola, B. L., Black, D. L., Brooks, A. N., Cheng, C., Conesa, A., Crosse, E. I., Eyras, E., Guccione, E., et al. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00750-2 · Cited by 48 · see citing works
The intersection of aging and estrogen in osteoarthritis
Atasoy‐Zeybek, A., Showel, K. K., Nagelli, C. V., Westendorf, J. J., & Evans, C. H. (2025) · npj Women s Health · doi:10.1038/s44294-025-00063-1 · Cited by 56 · see citing works
“Recent scienti fi c advances have identi fi ed fi ve additional aging characteristics that complement the original hallmarks: compromised autophagy, dysbiosis (microbiome disturbances), splicing dysregulation, in fl ammaging (chronic low-grade in fl ammation) and altered mechanical properties 38,39 .”
Aging, cellular senescence and Parkinson's disease
Ma, Y., Erb, M. L., & Moore, D. J. (2025) · Journal of Parkinson s Disease · doi:10.1177/1877718x251316552 · Cited by 45 · see citing works
“20,21 The antagonistic hallmarks of aging are cellular senescence, deregulated nutrient sensing and mitochondrial dysfunction.”
InfluentialMeasuring healthy ageing: current and future tools
Silva, N., Rajado, A. T., Esteves, F., Brito, D. V. C., Apolónio, J. D., Roberto, V. P., Binnie, A., Araújo, I. M., Nóbrega, C., Bragança, J., et al. (2023) · Biogerontology · doi:10.1007/s10522-023-10041-2 · Cited by 50 · see citing works
“These cellular effects lead to systemic age-related pathologies that are accompanied by loss of function and, ultimately, death (López–Otín et al. 2013; Schmauck-Medina et al. 2022; Singh et al. 2019a, b).”
BackgroundPun, F. W., Leung, G. H. D., Leung, H.-W., Rice, J., Schmauck‐Medina, T., Lautrup, S., Long, X., Liu, B. H. M., Wong, C. W., Ozerov, I. V., et al. (2023) · Aging Cell · doi:10.1111/acel.14017 · Cited by 42 · see citing works
“…Leung, et al., 2022 ), as well as compromised autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, processes associ - ated with extracellular matrix (ECM) stiffness, inflammation, and retrotransposition (Pun, Leung, et al., 2022 ; Schmauck-Medina et al., 2022 ).”
BackgroundSelf-citationPalikaras, K., Mari, M., Ploumi, C., Princz, A., Filippidis, G., & Tavernarakis, N. (2023) · Aging Cell · doi:10.1111/acel.13788 · Cited by 42 · see citing works
“Several hallmarks of aging are tightly associated with nuclear homeostasis (Hou et al., 2019; Lopez-Otin et al., 2013; Schmauck-Medina et al., 2022).”
BackgroundSoto, M. E., Pérez-Torres, I., Rubio-Ruiz, M. E., Cano-Martı́nez, A., Manzano-Pech, L., & Guarner‐Lans, V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054534 · Cited by 42 · see citing works
Chaudhari, D. S., Jain, S., Yata, V. K., Mishra, S. P., Kumar, A., Fraser, A., Kociolek, J., Dangiolo, M. B., Smith, A., Golden, A. G., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00799-1 · Cited by 42 · see citing works
“Emerging evidence suggests that abnormalities in gut microbiome may contribute to aging biology mechanisms [45].”
BackgroundTravagli, V., & Iorio, E. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108465 · Cited by 49 · see citing works
Aya, V., Jiménez, P., Muñoz, E., & Ramírez, J. D. (2023) · BMC Geriatrics · doi:10.1186/s12877-023-04066-y · Cited by 42 · see citing works
“However, recent studies of aging have planned new hallmarks compromising inflammation and microbiome disturbance, among others [5].”
BackgroundCross‐tissue comparison of epigenetic aging clocks in humans
Apsley, A. T., Ye, Q., Caspi, A., Chiaro, C. R., Etzel, L. C., Hastings, W. J., Heim, C. C., Kozlosky, J. T., Noll, J. G., Schreier, H. M. C., et al. (2025) · Aging Cell · doi:10.1111/acel.14451 · Cited by 42 · see citing works
“Measurements of biological age aim to capture the progressive deterioration of cells, tissues, and organs (López-Otín et al., 2013 ; Schmauck-Medina et al., 2022 ).”
Quan, J., Liu, Q., Li, P., Yang, Z., Zhang, Y., Zhao, F., & Zhu, G. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04160-5 · Cited by 42 · see citing works
“Consequently, researchers have explored new hallmarks of aging [4]: impaired autophagy [5], dysregulated microbiome, altered mechanical properties, splicing dysregulation, and chronic inflammation [6], integrating them with the original hallmarks for a more comprehensive understanding of aging…”
The contribution of mitochondrial DNA alterations to aging, cancer, and neurodegeneration
Picca, A., Guerra, F., Calvani, R., Coelho‐Júnior, H. J., Leeuwenburgh, C., Bucci, C., & Marzetti, E. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112203 · Cited by 39 · see citing works
Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?
Akusjärvi, S. S., & Neogi, U. (2023) · Current HIV/AIDS Reports · doi:10.1007/s11904-023-00646-0 · Cited by 38 · see citing works
The central role of DNA damage in immunosenescence
Kell, L., Simon, A. K., Alsaleh, G., & Cox, L. S. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1202152 · Cited by 38 · see citing works
“Autophagy is a process by which cells degrade excess or damaged intracellular proteins and larger cargo such as organelles; altered autophagy is recognised as a hallmark of ageing (Schmauck-Medina et al., 2022; Lopez-Otin et al., 2023).”
BackgroundSelf-citationRoig‐Rosello, E., Dayan, G., Bovio, S., Manissier, P., Errazuriz-Cerda, E., & Rousselle, P. (2024) · Aging Cell · doi:10.1111/acel.14096 · Cited by 38 · see citing works
Mitochondrion: A bridge linking aging and degenerative diseases
Zhang, L., Wu, J., Zhu, Z., He, Y., & Fang, R. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121666 · Cited by 38 · see citing works
The influence of inflammation and frailty in the aging continuum.
Arosio, B., Ferri, E., Mari, D., Tobaldini, E., Vitale, G., & Montano, N. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111872 · Cited by 37 · see citing works
Kritchevsky, S. B., & Cummings, S. R. (2025) · JAMA · doi:10.1001/jama.2025.11289 · Cited by 38 · see citing works
Hurvitz, N., Elkhateeb, N., Sigawi, T., Rinsky‐Halivni, L., & Ilan, Y. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.1044038 · Cited by 36 · see citing works
“Variability characterizes many of these processes (Lemoine, 2021; Schmauck-Medina et al., 2022).”
BackgroundGranic, A., Sayer, A. A., Cooper, R., & Robinson, S. M. (2024) · Proceedings of The Nutrition Society · doi:10.1017/s0029665124007432 · Cited by 35 · see citing works
“Chronic inflammation is an established hallmark of ageing (111,112) that, in connection with other hallmarks such as altered nutrient sensing (113) , drives many age-related processes and diseases (114) , including the inflammatory response in ageing muscle and sarcopenia (7,30,115,116) .”
Hoseinpour, A. N., Bassami, M., Ahmadizad, S., Donath, L., Setayesh, S., Mirzaei, M., & Rahimi, G. R. M. (2024) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2024.105731 · Cited by 35 · see citing works
Impacts of gut microbiota alteration on age-related chronic liver diseases
Adhikary, S., Esmeeta, A., Dey, A., Banerjee, A., Saha, B., Gopan, P., Duttaroy, A. K., & Pathak, S. (2023) · Digestive and Liver Disease · doi:10.1016/j.dld.2023.06.017 · Cited by 35 · see citing works
Młynarska, E., Kowalik, A., Krajewska, A., Krupińska, N., Marcinkowska, W., Motor, J., Przybylak, A., Tłustochowicz, K., Rysz, J., & Franczyk, B. (2025) · Biomolecules · doi:10.3390/biom15101452 · Cited by 35 · see citing works
“Hallmarks of aging [14–16].”
Aging and Oral Health: Biological and Sociobehavioral Perspectives
Colombo, A. P. V., & Wu, B. (2023) · Journal of Dental Research · doi:10.1177/00220345231181885 · Cited by 34 · see citing works
“Compromised autophagy was recently listed as a new integrative hallmark of aging (Schmauck-Medina et al. 2022).”
Cellular senescence and premature aging in Down Syndrome
Peng, L., Baradar, A. A., Aguado, J., & Wolvetang, E. J. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111824 · Cited by 34 · see citing works
Jiménez, A. G. (2023) · Biogerontology · doi:10.1007/s10522-023-10037-y · Cited by 32 · see citing works
Targeting the hallmarks of aging to improve influenza vaccine responses in older adults
Cadar, A. N., Martin, D. E., & Bartley, J. M. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00348-6 · Cited by 32 · see citing works
“Importantly, in 2022, 5 new proposed hallmarks were discussed among leaders in the aging research field including compromised autophagy, dysregulation in RNA splicing, inflammation, loss of cytoskeleton integrity and disturbance of the microbiome [85].”
BackgroundTargeting estrogen signaling and biosynthesis for aged skin repair
Zomer, H. D., & Cooke, P. S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1281071 · Cited by 34 · see citing works
Primary cilia shape hallmarks of health and aging
Silva, D. F., & Cavadas, C. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.04.001 · Cited by 31 · see citing works
Walzik, D., Jonas, W., Joisten, N., Belen, S., Wüst, R. C. I., Guillemin, G. J., & Zimmer, P. (2023) · Acta Physiologica · doi:10.1111/apha.13921 · Cited by 32 · see citing works
Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer’s Disease
Georgieva, I., Tchekalarova, J. D., Iliev, D. B., & Tzoneva, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411344 · Cited by 28 · see citing works
Vun, J. S. H., Iqbal, N., Jones, E., & Ganguly, P. (2023) · Bioengineering · doi:10.3390/bioengineering10080987 · Cited by 28 · see citing works
Kadyan, S., Park, G., Wang, B., Singh, P. R., Arjmandi, B. H., & Nagpal, R. (2023) · Scientific Reports · doi:10.1038/s41598-023-37036-w · Cited by 27 · see citing works
Complexity of Sex Differences and Their Impact on Alzheimer’s Disease
Kadlecová, M., Freude, K., & Haukedal, H. (2023) · Biomedicines · doi:10.3390/biomedicines11051261 · Cited by 26 · see citing works
Cellular senescence and frailty: a comprehensive insight into the causal links
Marcozzi, S., Bigossi, G., Giuliani, M. E., Giacconi, R., Piacenza, F., Cardelli, M., Brunetti, D., Segala, A., Valerio, A., Nisoli, E., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00960-w · Cited by 24 · see citing works
“Although cellular senescence is not a primary hallmark of aging [61] [15], senescent cells can represent a source of damage that is able to rapidly propagate resembling a contagious process [62].”
BackgroundBody-wide multi-omic counteraction of aging with GLP-1R agonism
Huang, J., Kwok, A. J., Li, J. C. Y., Chiu, C. L. H., Ip, B. Y. M., Tung, L. Y., Chan, R. C. H., Chan, D. T.-M., Wang, Z., Zheng, X., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.10.014 · Cited by 31 · see citing works
Self-citationDifferent Aspects of Aging in Migraine
Fila, M., Pawłowska, E., Szczepańska, J., & Błasiak, J. (2023) · Aging and Disease · doi:10.14336/ad.2023.0313 · Cited by 24 · see citing works
“Stem cells play an important role in organismal aging and stem cell exhaustion is a well-established molecular marker of aging [10].”
BackgroundInfluentialMitochondrial transplantation as a possible therapeutic option for sarcopenia
Türkel, İ., Özerkliğ, B., Yılmaz, M., Ülger, Ö., Kubat, G. B., & Tuncer, M. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02326-3 · Cited by 24 · see citing works
Exploring the Prospective Role of Propolis in Modifying Aging Hallmarks
Scorza, C. A., Gonçalves, V., Finsterer, J., Scorza, F. A., & Fonseca, F. L. A. (2024) · Cells · doi:10.3390/cells13050390 · Cited by 24 · see citing works
Cerantonio, A., Citrigno, L., Greco, B. M., Benedittis, S. D., Passarino, G., Maletta, R., Qualtieri, A., Montesanto, A., Spadafora, P., & Cavalcanti, F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116062 · Cited by 23 · see citing works
Picca, A., Triolo, M., Wohlgemuth, S. E., Martenson, M. S., Mankowski, R. T., Anton, S. D., Marzetti, E., Leeuwenburgh, C., & Hood, D. A. (2023) · Cells · doi:10.3390/cells12010183 · Cited by 23 · see citing works
“Notably, mitochondrial dysfunction and mitophagy alterations are acknowledged as hallmarks of aging [36].”
BackgroundThe Double-Edged Role of Extracellular Vesicles in the Hallmarks of Aging
Romero-García, N., Huete-Acevedo, J., Mas‐Bargues, C., Sanz‐Ros, J., Dromant, M., & Borrás, C. (2023) · Biomolecules · doi:10.3390/biom13010165 · Cited by 23 · see citing works
New insight into the causes, consequences, and correction of hematopoietic stem cell aging
Mansell, E., Lin, D. S. Y., Loughran, S. J., Milsom, M. D., & Trowbridge, J. J. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.07.002 · Cited by 21 · see citing works
Self-citationSuppression of thrombospondin-1–mediated inflammaging prolongs hematopoietic health span
Ramalingam, P., Gutkin, M. C., Poulos, M. G., Winiarski, A., Smith, A., Carter, C., Doughty, C., Tillery, T., Redmond, D., Freire, A. G., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.ads1556 · Cited by 17 · see citing works
Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues
Rolas, L., Stein, M., Barkaway, A., Reglero-Real, N., Sciacca, E., Yaseen, M., Wang, H., Vázquez-Martínez, L., Golding, M., Blacksell, I. A., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00182-x · Cited by 21 · see citing works
“Of relevance, we have previously shown that compromised EC autophagy, a hallmark of aging (Schmauck-Medina et al, 2022), induces excessive neutrophil in fi ltration in multiple models of acute in fl ammation (Reglero-Real et al, 2021).”
BackgroundVučić, V., Ristić-Medić, D., Arsić, A., Petrović, S., Paunović, M., Vasiljević, N., & Ilich, J. Z. (2023) · Nutrients · doi:10.3390/nu15071619 · Cited by 20 · see citing works
The role of cannabidiol in aging
Ni, B., Liu, Y., Dai, M., Zhao, J., Yu, L., Yang, X. C., Han, B., & Jiang, M. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115074 · Cited by 21 · see citing works
The link between obesity and aging - insights into cardiac energy metabolism
Owesny, P., & Grune, T. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111870 · Cited by 21 · see citing works
“All these hallmarks represent essential factors in the aging process, and the interplay between them can ultimately determine the health outcomes of older individuals (L ´ opez-Otín et al., 2013; Calabrese et al., 2015; Schmauck-Medina et al., 2022).”
BackgroundComparative lifespan and healthspan of nonhuman primate species common to biomedical research
Huber, H. F., Ainsworth, H. C., Quillen, E. E., Salmon, A., Ross, C. N., Azhar, A. D., Bales, K. L., Basso, M. A., Coleman, K., Colman, R. J., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01421-8 · Cited by 20 · see citing works
“Five new hallmarks have been recently proposed: autophagy, micro-biome disturbance, altered mechanical properties, splicing dysregulation, and inflammation [48].”
Self-citationFunctional Aging: Integrating Functionality to a Multidimensional Assessment of Healthy Aging
Frangos, E., Graf, C., & Samaras, N. (2023) · Current Gerontology and Geriatrics Research · doi:10.1155/2023/9409918 · Cited by 18 · see citing works
“Indeed, the hallmarks of aging, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, compromised autophagy, microbiome disturbance, al…”
BackgroundAortic Stiffness: A Major Risk Factor for Multimorbidity in the Elderly
Triposkiadis, F. K., Xanthopoulos, A. V., Lampropoulos, K. M., Briasoulis, Α., Sarafidis, P. A., Skoularigis, J. S., & Boudoulas, H. K. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12062321 · Cited by 23 · see citing works
Kumar, P., Osahon, O. W., & Sekhar, R. V. (2023) · Antioxidants · doi:10.3390/antiox12051042 · Cited by 20 · see citing works
A revisiting of “the hallmarks of aging” in domestic dogs: current status of the literature
Jiménez, A. G. (2023) · GeroScience · doi:10.1007/s11357-023-00911-5 · Cited by 20 · see citing works
“Each of the biomarkers of the hallmarks of aging described in López-Otín et al. [93] and Schmauck-Medina et al. [124] was searched, in turn, with “and dogs” and “and canines” using googlescholar.com.”
InfluentialRepurposing digoxin for geroprotection in patients with frailty and multimorbidity
Lee, H., Wilson, D. V., Bunting, K. V., Kotecha, D., & Jackson, T. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101860 · Cited by 19 · see citing works
Bensalem, J., Teong, X. T., Hattersley, K. J., Hein, L. K., Fourrier, C., Liu, K., Hutchison, A. T., Heilbronn, L. K., & Sargeant, T. J. (2023) · GeroScience · doi:10.1007/s11357-023-00884-5 · Cited by 19 · see citing works
“In this way, autophagy limits cell damage and slows biological aging [1], and autophagic dysfunction itself has recently been discussed as a hallmark of aging [2].”
BackgroundCardiac iron metabolism during aging – Role of inflammation and proteolysis
Walter, S., Mertens, C., Muckenthaler, M. U., & Ott, C. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111869 · Cited by 19 · see citing works
The Use of Gut Microbial Modulation Strategies as Interventional Strategies for Ageing
Siddiqui, R., Mungroo, M. R., Alharbi, A. M., Alfahemi, H. H., & Khan, N. A. (2022) · Microorganisms · doi:10.3390/microorganisms10091869 · Cited by 19 · see citing works
“In this regard, the disturbance of the microbiome has been suggested as a new hallmark of ageing in the recent meeting held in Copenhagen on March 2022, in addition to the original nine hallmarks of ageing proposed by López-Otín and colleagues in 2013 [13].”
BackgroundTargeting multiple hallmarks of mammalian aging with combinations of interventions
Panchin, A. Y., Ogmen, A., Blagodatski, A. S., Egorova, A., Batin, M., & Glinin, T. S. (2024) · Aging · doi:10.18632/aging.206078 · Cited by 20 · see citing works
The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease
Ayoub, M., Jaoude, C. A., Ayoub, M., Hamadé, A., & Rima, M. (2025) · Immunology · doi:10.1111/imm.70036 · Cited by 22 · see citing works
Xiong, W., Li, R., Li, B., Wang, X., Wang, H. H., Sun, Y., Wang, X., Li, Y., & Ren, F. (2023) · Nutrients · doi:10.3390/nu15092228 · Cited by 19 · see citing works
Autophagy and metabolic aging: Current understanding and future applications
Raza, S. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119753 · Cited by 19 · see citing works
Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging
Görgün, C., Africano, C., Ciferri, M. C., Bertola, N., Reverberi, D., Quarto, R., Ravera, S., & Tasso, R. (2022) · Cells · doi:10.3390/cells11223695 · Cited by 18 · see citing works
Relationships between circulating metabolites and facial skin aging: a Mendelian randomization study
Liu, Z., Mi, J., & Wu, H. (2023) · Human Genomics · doi:10.1186/s40246-023-00470-y · Cited by 18 · see citing works
“The process of skin aging is affected by circulating metabolites which are involved in a variety of cellular processes including cellular organization, post-translational modification as well as epigenetic changes [4, 5].”
BackgroundNurturing longevity through natural compounds: Where do we stand, and where do we go?
Todorova, M. N., Savova, M. S., Mihaylova, L. V., & Georgiev, M. I. (2024) · Food Frontiers · doi:10.1002/fft2.350 · Cited by 17 · see citing works
Aryl hydrocarbon receptor: Linking environment to aging process in elderly patients with asthma
Yang, T., Wan, R., Tu, W., Avvaru, S. N., & Gao, P. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002960 · Cited by 17 · see citing works
“[13,14] The updated hallmarks of aging may provide a better guide and advanced research on the biology of aging, as illustrated in Figure 1.”
BackgroundParticulate matter 2.5 accelerates aging: Exploring cellular senescence and age-related diseases.
Wang, S.-N., Shi, Y.-C., Lin, S., & He, H.-F. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116920 · Cited by 19 · see citing works
Ai, R., Mao, L., Jin, X., Campos‐Marques, C., Zhang, S., Pan, J., Lagartos-Donate, M. J., Cao, S., Barros‐Santos, B., Nóbrega‐Martins, R., et al. (2025) · Science Advances · doi:10.1126/sciadv.ady9811 · Cited by 19 · see citing works
“We found that ASEs in genes involved in RNA splicing are disproportionately dysregulated in tauopathies and aging worms, which is in line with the publications showing that ASE is a mark of aging and neurodegenerative disease ( 117–120 ).”
Self-citation
- Authors
- Schmauck-Medina, T., Molière, A., Lautrup, S., Zhang, J., Chlopicki, S., Madsen, H. B., Cao, S., Soendenbroe, C., Mansell, E., Vestergaard, M. B., Li, Z., Shiloh, Y., Opresko, P. L., Egly, J.-M., Kirkwood, T., Verdin, E., Bohr, V. A., Cox, L. S., Stevnsner, T., Rasmussen, L. J., & Fang, E. F.
- Affiliations
- Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog 1478, Norway
- University of Oslo (NO)
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow 30-348, Poland
- University of Copenhagen (DK)
- Bispebjerg Hospital (DK)
- Lund University (SE)
- Copenhagen University Hospital (DK)
- Tel Aviv University (IL)
- University of Pittsburgh (US)
- Centre National de la Recherche Scientifique (FR)
- Buck Institute for Research on Aging (US)
- University of Oxford (GB)
- Aarhus University (DK)
- Corresponding author
- Stevnsner, Tinna
- Rasmussen, Lene Juel
- Fang, Evandro F.
- ORCID
- Molière, Adrian
- Lautrup, Sofie
- Zhang, Jianying
- Madsen, Helena Borland
- Cao, Shuqin
- Soendenbroe, Casper
- Mansell, Els
- Vestergaard, Mark Bitsch
- Li, Zhiquan
- Shiloh, Yosef
- Opresko, Patricia L.
- Egly, Jean-Marc
- Kirkwood, Thomas
- Verdin, Eric
- Bohr, Vilhelm A.
- Cox, Lynne S.
- Stevnsner, Tinna
- Rasmussen, Lene Juel
- Fang, Evandro F.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2022-08-29
- Volume
- 14
- Issue
- 16
- Pages
- 6829-6839
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC9467401
- OpenAlex
- W4293462467
- Cited by
- 319
- References
- 58
- Citations by year
- 2026: 42 · 2025: 67 · 2024: 100 · 2023: 102 · 2022: 8
- FWCI
- 23.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- HAL (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Lundbeckfonden (R347-2020-2176)
- Novo Nordisk
- Biotechnology and Biological Sciences Research Council (BB/W01825X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- hallmarks of aging, aging, autophagy, microbiome, mechanical properties, splicing dysregulation, inflammation, age-related diseases, cellular senescence, stem cell exhaustion, intercellular communication, proteostasis, nutrient sensing, telomere shortening, epigenetic modifications, mitochondrial dysfunction, genomic instability
- MeSH terms
- Aged, Aging, Humans, Telomere, Cellular Senescence, Genomic Instability, Epigenesis, Genetic
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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