Table 1.

CHIP studies involving aged individuals.

Subjects	Frequency of CHIP	Mutations in CHIP	Main features of individuals with CHIP
Normal healthy subjects (Jaswal et al. 2014) 17,182 healthy persons Whole exome sequencing	Variable following age (yr) 20–29 0%; 30–39 0,.1% 40–49 1.7%; 50–59 2.5% 60–69 5.6%; 70–79 9.5% 80–89 11.6%; 90–99 16% 100–108 29%	DNMT33A (59%), TET2 (10.6%), ASXL1 (9.1%), TP53 (4.9%), JAK2 (4.5%) SF3B1 (3.9%), GNB1 (3.2%), CBL (1.8%), SRSF2 (1.6%) 93% with 1 mutation, 7% with two mutations	Individuals with CHIP with 1 or 2 mutations he hematologic parameters comparable to those of individuals without CHIP. Among individuals with a VAF of ≥0.1 the risk of developing a hematologic cancer is increased by a factor nearly 50. Individuals with CHIP who were 70 years of age or older have an increased risk of death related to hematologic neoplasms and to an increased incidence of cardiovascular diseases.
Normal healthy subjects (Zink et al. 2017) 11,262 Icelanders Whole genome sequencing	12.5 in the whole population, variable with age, reaching a frequency of 23%, 32% and 52% in the age groups of 65–75, 75–85 and 85–110 years, respectively.	The most frequent mutations occurred at the level of DNMT3a; TET2, ASXL1, PPM1D, JAK2, TP53, SRSF2 and SF3B1.	In this population the presence of CHIP was associated with higher death rates and increased risk of hematological malignancy.
Individuals aged ≥80 years (van Zeventer et al. 2021) Targeted errorcorrected NGS at a VAF ≥1%	62% Variable following age, from 57% in the 80–82 years to 72% in the ≥86 years group.	DNMT3A 35% TET2 27% ASXL1 6% Spliceosome 4% TP53 3% Multiple variants of DNMT3A and TET2 are frequently observed.	No effect of CHIP on hematologic parameters. No differences in the incidence of CHIP related to the sex. An elevated risk of exposure to DNA damaging agents was not significantly associated with differences in the prevalence of CHIP; however, ASXL1 and spliceosome gene variants are more frequent in these individuals. No association with cardiovascular diseases, but with COPD was observed. Overall, CHIP did not confer an increased risk of death; however, individuals with multiple genetic variants have an increased risk of death and of developing hematologic malignancies.
299 twin pairs ≥70 years (Hansen et al. 2020) Targeted NGS covering CHIP mutations	36% Variable following age, from 29% at 75 yrs to >64% in the group >85 years.	DNMT3A 48.5% TET2 38% ASXL1 10% TP53 5% PPM1D 4% JAK2 3.5%	20 twin pairs had mutations within the same genes but the exact same mutation was observed in only 2 twin pairs. No differences in casewise concordance between monozygotic and dizygotic twins was observed for any gene, subgroup, or CHIP mutations overall, and no significant heritability was detected. 127 twin pairs were discordant for at least mutation, and in 48% of these cases, the affected twin died first.
1794 individuals aged >80 years. (Rossi et al. 2021) Targeted NGScovering CHIP mutations	32.6%	DNMT3A, TET2, ASXL1, PPM1D, SF3B1, BCOR, JAK2, TP53 were the most recurrently mutated.	TET2, DNMT3A and ASXL1 comutations, splicing gene mutations and VAF> 0.096 are independent preditictor for developing myeloid neoplasms. ASXL1, TET2, DNMT3A and JAK2 mutations are high-risk for vascular events. The individuals with cytopenias and with CHIP bearing splicing genes, ASXL1, DNMT3A or TET2 comutations and/or VAF >0.096 have a high-risk of leukemic transformation.