1. Antonarakis, S. E. et al. Down syndrome. Nat. Rev. Dis. Prim. 6, 1–20 (2020).
2. Epstein, C. J. 2001 William Allan award address from down syndrome to the ‘Human’ in ‘Human Genetics’. Am. J. Hum. Genet. 70, 300–313 (2002).
3. Wiseman, F. K. et al. A genetic cause of Alzheimer disease: Mechanistic insights from Down syndrome. Nat. Rev. Neurosci. 16, 564–574 (2015).
4. Hithersay, R. et al. Association of Dementia with Mortality among Adults with Down Syndrome Older Than 35 Years. JAMA Neurol. 76, 152–160 (2019).
5. Cuadrado, E. & Barrena, M. J. Immune dysfunction in Down’s syndrome: Primary immune deficiency or early senescence of the immune system? Clin. Immunol. Immunopathol. 78, 209–214 (1996).
6. da Silva, V. Z. M. et al. Bone mineral density and respiratory muscle strength in male individuals with mental retardation (with and without Down Syndrome). Res. Dev. Disabil. 31, 1585–1589 (2010).
7. Komatsu, T. et al. Reactive oxygen species generation in gingival fibroblasts of Down syndrome patients detected by electron spin resonance spectroscopy. Redox Rep. 11, 71–77 (2006).
8. Roizen, N. J. & Patterson, D. Down’s syndrome. Down’s Syndr. 361, 1281–9 (2003).
9. Doran, E. et al. Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer’s Disease: The Role of APP. J Alzheimers Dis. 56, 459–470 (2017).
10. Prasher, V. P. et al. Molecular mapping of Alzheimer-type dementia in Down’s syndrome. Ann. Neurol. 43, 380–383 (1998).
11. Head, E., Silverman, W., Patterson, D. & Lott, I. T. Aging and down syndrome. Curr. Gerontol. Geriatr. Res. 2012, (2012).
12. Nižetić, D. & Groet, J. Tumorigenesis in Down’s syndrome: Big lessons from a small chromosome. Nat. Rev. Cancer 12, 721–732 (2012).
13. Busciglio, G. & Yankner, B. Apoptosis and increased generation of ROS in DS neurons in vitro. Nature 378, 776–779 (1995).
14. Murray, A. et al. Isogenic induced pluripotent stem cell lines from an adult with mosaic Down Syndrome model accelerated neuronal ageing and neurodegeneration. Stem Cells 33, 2077–2084 (2015).
15. Del Bo, R. et al. Down’s syndrome fibroblasts anticipate the accumulation of specific ageing-related mtDNA mutations. Ann. Neurol. 49, 137–8 (2001).
16. Druzhyna, N., Nair, R. G., Ledoux, S. P. & Wilson, G. L. Defective repair of oxidative damage in mitochondrial DNA in Down’s syndrome. Mutat. Res. - DNA Repair 409, 81–89 (1998).
17. Necchi, D. et al. Defective DNA repair and increased chromatin binding of DNA repair factors in Down syndrome fibroblasts. Mutat. Res. - Fundam. Mol. Mech. Mutagen. 780, 15–23 (2015).
18. Raji, N. S. & Rao, K. S. Trisomy 21 and accelerated aging: DNA-repair parameters in peripheral lymphocytes of Down’s syndrome patients. Mech. Ageing Dev. 100, 85–101 (1998).
19. Amiel, A., Goldzak, G., Gaber, E. & Fejgin, M. D. Molecular cytogenetic characteristics of Down syndrome newborns. J. Hum. Genet. 51, 541–547 (2006).
20. Zana, M. et al. Age-dependent oxidative stress-induced DNA damage in Down’s lymphocytes. Biochem. Biophys. Res. Commun. 345, 726–733 (2006).
21. Morawiec, Z. et al. DNA damage and repair in children with Down’s syndrome. Mutat. Res. - Fundam. Mol. Mech. Mutagen. 637, 118–123 (2008).
22. Thomas, P., Harvey, S., Gruner, T. & Fenech, M. The buccal cytome and micronucleus frequency is substantially altered in Down’s syndrome and normal ageing compared to young healthy controls. Mutat. Res. - Fundam. Mol. Mech. Mutagen. 638, 37–47 (2008).
23. Ishihara, K. et al. Increased lipid peroxidation in Down’s syndrome mouse models. J. Neurochem. 110, 1965–1976 (2009).
24. Wang, Y. et al. Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks. Radiat. Res. 185, 630–637 (2016).
25. Hadi, E. et al. Telomere aggregates in trisomy 21 amniocytes. Cancer Genet. Cytogenet. 195, 23–26 (2009).
26. Cobb, B. A. The history of IgG glycosylation and where we are now. Glycobiology 30, 202–213 (2020).
27. Gudelj, I., Lauc, G. & Pezer, M. Immunoglobulin G glycosylation in aging and diseases. Cell. Immunol. 333, 65–79 (2018).
28. Krištić, J. et al. Glycans are a novel biomarker of chronological and biological ages. Journals Gerontol. - Ser. A Biol. Sci. Med. Sci. 69, 779–789 (2014).
29. Horvath, S. et al. Accelerated epigenetic aging in Down syndrome. Aging Cell 14, 491–495 (2015).
30. Hanić, M., Lauc, G. & Trbojević-Akmačić, I. N-Glycan Analysis by Ultra-Performance Liquid Chromatography and Capillary Gel Electrophoresis with Fluorescent Labeling. Curr. Protoc. Protein Sci. 97, 1–21 (2019).
31. Trbojević-Akmačić, I., Ugrina, I. & Lauc, G. Comparative Analysis and Validation of Different Steps in Glycomics Studies. Methods Enzymol. 586, 37–55 (2017).
32. Petrović, T. et al. Composition of the immunoglobulin G glycome associates with the severity of COVID-19. Glycobiology cwaa102. (2020).
33. Martin, T. C. et al. Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases. Mol Cell Proteomics 19, 774–792 (2020).
34. Cvetko, A. et al. Glycosylation alterations in multiple sclerosis show increased proinflammatory potential. Biomedicines 8, 1–14 (2020).
35. Gudelj, I. et al. Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up. Biochim. Biophys. Acta - Mol. Basis Dis. 1864, 2034–2039 (2018).
36. Menni, C. et al. Glycosylation Profile of Immunoglobulin G Is Cross-Sectionally Associated with Cardiovascular Disease Risk Score and Subclinical Atherosclerosis in Two Independent Cohorts. Circ. Res. 122, 1555–1564 (2018).
37. Vučković, F. et al. Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome. Arthritis Rheumatol. 67, 2978–2989 (2015).
38. Mann, D. M. A. Alzheimer’s disease and Down’s syndrome. Histopathology 13, 125–137 (1988).
39. Chistiakov, D. Down syndrome and coexistent autoimmune diseases. J. Appl. Biomed. 5, 71–76 (2007).
40. Štambuk, J. et al. Global variability of the human IgG glycome. Aging (Albany. NY). 12, 15222–15259 (2020).
41. Franceschi, C. et al. Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies. Aging Cell 18, 1–11 (2019).
42. Delabar, J. M. et al. Molecular mapping of twenty-four features of Down syndrome on chromosome 21. European journal of human genetics : EJHG 1, 114–124 (1993).
43. Korenberg, J. R. et al. Molecular definition of a region of chromosome 21 that causes features of the down syndrome phenotype. Am. J. Hum. Genet. 47, 236–246 (1990).
44. Fumagalli, M. & d’Adda di Fagagna, F. SASPense and DDRama in cancer and ageing. Nat. Cell Biol. 11, 921–923 (2009).
45. Shapiro, B. L. Down Syndrome-A Homeostasis. Am J Med Genet 14, 241–269 (1983).
46. Antonarakis, S. E., Lyle, R., Dermitzakis, E. T., Reymond, A. & Deutsch, S. Chromosome 21 and Down syndrome: From genomics to pathophysiology. Nat. Rev. Genet. 5, 725–738 (2004).
47. Jenkins, E. C. et al. Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome. Am. J. Med. Genet. 68, 147–151 (1997).
48. Percy, M. E. et al. Age-associated chromosome 21 loss in Down syndrome: Possible relevance to mosaicism and Alzheimer disease. Am. J. Med. Genet. 45, 584–588 (1993).
49. Lightfoot, D. A. & Höög, C. Low level chromosome instability in embryonic cells of primary aneuploid mice. Cytogenet. Genome Res. 107, 95–98 (2004).
50. Reish, O., Regev, M., Kanesky, A., Girafi, S. & Mashevich, M. Sporadic aneuploidy in PHA-stimulated lymphocytes of trisomies 21, 18, and 13. Cytogenet. Genome Res. 133, 184–189 (2011).
51. Fujita, H. et al. Premature aging syndrome showing random chromosome number instabilities with CDC20 mutation. Aging Cell 19, 1–13 (2020).
52. Kazuki, Y. et al. A non-mosaic transchromosomic mouse model of down syndrome carrying the long arm of human chromosome 21. Elife 9, 1–29 (2020).
53. O’Doherty, A. et al. An Aneuploid Mouse Strain Carrying Human Chromosome 21 with Down Syndrome Phenotypes. Science (80-. ). 309, 2033–2037 (2005).
54. Busciglio, J. et al. Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron 33, 677–688 (2002).
55. De Haan, J. B. et al. Elevation in the ratio of Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide. Hum. Mol. Genet. 5, 283–292 (1996).
56. Adorno, M. et al. Usp16 contributes to somatic stem-cell defects in Down’s syndrome. Nature 501, 380–384 (2013).
57. Guard, S. E. et al. The nuclear interactome of DYRK1A reveals a functional role in DNA damage repair. Sci. Rep. 9, 1–12 (2019).
58. Menon, R. et al. DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169. Cell Cycle 18, 531–551 (2019).
59. Roewenstrunk, J. et al. A comprehensive proteomics-based interaction screen that links DYRK1A to RNF169 and to the DNA damage response. Sci. Rep. 9, 1–14 (2019).
60. Borelli, V. et al. Plasma N-Glycome Signature of Down Syndrome. J. Proteome Res. 14, 4232–4245 (2015).
61. Relja, A. et al. Nut consumption and cardiovascular risk factors: A cross-sectional study in a mediterranean population. Nutrients 9, 1–20 (2017).
62. Rudan, I. et al. ‘10 001 Dalmatians:’ Croatia Launches Its National Biobank. Croat. Med. J. 50, 4–6 (2009).
63. Dagostino, C. et al. Validation of standard operating procedures in a multicenter retrospective study to identify-omics biomarkers for chronic low back pain. PLoS One 12, (2017).
64. Verdi, S. et al. TwinsUK: The UK Adult Twin Registry Update. Twin Res. Hum. Genet. 22, 523–529 (2019).
65. Andrew, T. et al. Are twins and singletons comparable? A study of disease-related and lifestyle characteristics in adult women. Twin Res. 4, 464–477 (2001).
66. Pezer, M. et al. Effects of allergic diseases and age on the composition of serum IgG glycome in children. Sci. Rep. 6, 1–10 (2016).
67. Lyle, R. et al. Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21. Eur. J. Hum. Genet. 17, 454–466 (2009).
68. Ugrina, I., Campbell, H. & Vučković, F. Laboratory Experimental Design for a Glycomic Study. in Methods Mol Biol. (eds. Lauc, G. & Wuhrer, M.) 13–19 (Humana Press, New York, NY, 2017).
69. Pucic, M. et al. High throughput isolation and glycosylation analysis of IgG-variability and heritability of the IgG glycome in three isolated human populations. Mol Cell Proteomics 10, M111.010090 (2011).