Table 2.

GIN and CIN (SGV) Associated with Normal Human Aging and Aging Diseases

Condition	Tissue/Cell Types	Overview of Instability	Key Refs
Natural genomic variations during normal aging
Normal aging	Blood lymphocytes	Chromosome X: 1.5%-2.5% and 4.5%-7.3%*; Chromosome Y loss: 0.17%; Autosomes: 1.2% and 1-2%*	[20, 36, 37, 39]
	Skin fibroblasts	2,2% and 4,4%*	[38]
	Brain	0.3-0.9% and 1.4-3%* (no targeted studies of the aging brain are, as yet, available)	[5, 10, 16, 18, 22, 33]
Aneuploidy and aneuploidy-associated/aging diseases
Aneuploidy	Aneuploid cell lines	Aneuploid cells demonstrate senescent phenotypes	[42]
Down syndrome(trisomy 21)	Blood lymphocytes (other tissues are rarely analyzed)	100% (?) of cells with additional chromosome 21 cause accelerated aging phenotype	[17, 25, 43]
AT	Brain	Aneuploidy and chromosome breakage producing additional rearranged chromosomes (partial aneuploidy) confine to the degenerated cerebellum and affect up to 40% of cells	[18, 33]
AD	Brain	Chromosome 21 aneuploidy affecting 6-15% of brain cells	[18]
	Transfected human presenelin1-mutated cells	Acquired chromosome missegregation causing aneuploidy associated with abnormal presenelin 1 functioning	[44]
	Transgenic mice and transfected human cells	Amyloid precursor protein gene (APP) induce chromosome missegregation and aneuploidy	[45]
Cancers	Almost all types of malignant tissues/cells	Aneuploidy hallmarks almost all cancers; aneuploid cells exhibit senescent phenotype	[14, 21, 40, 41]

^*— middle age and aged individuals, respectively.