Table 2. Human genome instability diseases with age-associated symptoms.

Disease	Affected genome stability pathway	Mutated genes	Aging-associated symptoms	Ref(s)
Hutchinson-Guilford progeria syndrome	Chromatin organization	LMNA	Alopecia, atherosclerosis, arthritis, cardiovascular disease, lipodystrophy, osteoporosis, skin aging and atrophy	Kudlow et al., 2007; Liu et al., 2005
Nestor-Guillermo progeria syndrome	Chromatin organization	BANF1	Alopecia, atherosclerosis, arthritis, cardiovascular disease, lipodystrophy, osteoporosis, and pulmonary hypertension	Cabanillas et al., 2011; Loi et al., 2016
Werner syndrome	Telomeric maintenance and replication stress	WRN	Alopecia, atherosclerosis, arthritis, cardiovascular disease, cataracts, diabetes, sarcopenia, and increased risk of cancer	Kudlow et al., 2007; Sugimoto, 2014
Rothmund-Thomson syndrome	DNA replication initiation	RECQL4	Alopecia, cataracts, osteoporosis, skin atrophy, and increased risk of cancer	Croteau et al., 2012; Ghosh et al., 2012
Bloom syndrome	DNA replication and recombination	BLM	Diabetes, pulmonary disease, increased risk of cancer	Hanada and Hickson, 2007; de Renty and Ellis, 2017
XFE progeroid syndrome	NER, ICL, and DSB repair	ERCC4	Anemia, cardiovascular disease, kidney disease, neurodegeneration, osteoporosis, sarcopenia, sensory loss, and skin atrophy	Niedernhofer et al., 2006
Xeroderma pigmentosum	NER and translesion DNA synthesis	XPA-G, XPV	Premature skin photoaging, neurodegeneration, and increased incidence of skin cancer	Lehmann et al., 2011; Kraemer and DiGiovanna, 2015
Cockayne syndrome	Transcription-coupled NER	CSA, CSB, XPB, XPD, XPG	Ataxia, cataracts, muscle atrophy, and neurodegeneration	Nance and Berry, 1992; Wilson et al., 2016
Trichothiodystrophy	Transcription-coupled NER	TTDA, TTDN1, XPB, XPD	Premature bone marrow exhaustion and increased risk of cancer	Faghri et al., 2008; de Boer et al., 2002
Fanconi anemia	ICL repair	FANCA-FANCW	Premature bone marrow exhaustion and increased risk of cancer	Ceccaldi et al., 2016; Nalepa and Clapp, 2018
Ataxia telangiectasia	DNA damage response	ATM	Premature bone marrow exhaustion, diabetes, and neurodegeneration	Rothblum-Oviatt et al., 2016
Mandibular hypoplasia, deafness, progeroid features, lipodystrophy syndrome	Post-replication repair and translesion DNA synthesis	POLD1	Diabetes, lipodystrophy, osteoporosis, steatosis, sensory loss	Weedon et al., 2013
Ruijs-Aalfs syndrome	Protein-DNA crosslink repair	SPRTN	Alopecia, atherosclerosis, cataracts, diabetes, premature graying of hair, osteoporosis, sarcopenia, and increased risk of cancer	Lessel et al., 2014
Alpers-Huttenlocher syndrome	Mitochondrial DNA replication and repair	POLG1	Progressive neurodegeneration and liver disease	Nguyen et al., 2006