Introduction
Factor | Reference | Age prediction model (referring to chronological (c), biological (b), phenotypic (p) age) | K | Information on investigated populations (as far as available) | Influence on the estimation of chronological age |
---|---|---|---|---|---|
Trauma/PTSD /lifetime stress | b | [16]: n = 281 veterans of the conflicts in Iraq and Afghanistan [17]: n = 339 trauma-exposed veterans [18]: review [20]: metastudy of several cohorts; n = 855 lifetime PTSD versus n = 516 lifetime controls, n = 876 current PTSD versus n = 1228 controls | Inconsistent; ↑ (trend; ~ 2 years) | ||
Low socioeconomic status/education | cell-count enriched Hannum clockc | b, s, l, m, mn | [22]: n = 100 women of African ancestry; 17.8% less than a 12th grade education [23]: n = 1594 subjects with low versus n = 1744 with high socioeconomic status (participants of three large prospective cohorts) [24]: n = 101 African American children (6–13 years old); 56,6% with low, versus 9,1% with high parents’ income; 57,7% with low 5% with high education level [25]: n = 932 persons (aged 16 years or more) [26]: life-course social economic status trajectory: n = 96 low/low, n = 85 low/high, n = 67 high/low, n = 87 high/high socioeconomic status [27]: multi-cohort study, 16,245 individuals [29]: 539 women with low versus 240 women with high education [30]: n = 287 children with versus n = 669 without financial hardship; n = 144 with versus n = 829 without neighbourhood disadvantages; 3.5–7 years old [31]: 27 cohort studies with a total of 10,767 individuals [33]: 458 women with low versus 1282 women with high education | ↑ (up to 1.85 years) | |
Experience of violence during childhood | s, b | [24]: n = 93 children with violence exposure (6–13 years old) [34]: n = 247 children/adolescents (8–16 years old) with wide variability in early lifetime adversity exposure [35]: multi-cohort study; n = 616, 20 and 22 years old | ↑ | ||
Cancer (several types) | [41]: Weidner clock (3 CpGs)b [12]: MIR29B2C/C1orf132c, TRIM59c, KFL14c | b/l | [2]: multi-data-set study of different tissues (healthy and diverse diseases, i.e. cancer) [12]: n = 39 patients with chronic lymphatic leukaemia versus 92 healthy controls [36]: n = 835 with colorectal cancer, n = 170 with gastric cancer, n = 143 with kidney cancer, n = 332 with lung cancer, n = 869 with prostate cancer, n = 439 with B cell lymphomas, n = 428 with urothelial cell carcinoma (aged between 27 and 76 years) [37]: n = 1864 older adults aged 50–75 years [39]: n = 451 female breast cancer patients versus 451 healthy controls [40]: n = 2029 women between the ages of 50–79 years [41]: n = 421 patients with diverse cancers versus 424 controls | ↑ (up to 2.5 years) | |
Obesity/high BMI/blood cholesterol levels | b, bc, s | [27]: multi-cohort study, 16,245 individuals [29]: n = 1206 women [32]: n = 5200 [42]: n = 183; longitudinal study [43]: n = 790 women [44]: n = 72 women with normal (< 24.9), n = 58 overweight (BMI 25–29.9) and n = 102 obese (BMI ≥ 30) women | ↑ (up to 1.08 year / 0.14 years per 1 kg/m2 increase in BMI) | ||
Infectious diseases | Horvath (353 CpGs) c | b | [45]: 3 datasets of HIV-infected (n = 156) versus 5 datasets from uninfected healthy subjects [46]: 137 HIV-infected vs. 44 healthy males | HIV: ↑ (4.9/5.2 years) | |
[47] | b | n = 122 nonagenerians (cytomegalovirus (CMV) seropositivity rate 95%); n = 21 young controls (CMV seropositivity rate 57%) | CMV: ↑ (up to 6 years) | ||
[48] | Horvath (353 CpGs) c, Hannum (71 CpGs) c | b | n = 765 Helicobacter pylori infected versus n = 712 uninfected | ↑ (up to 1 year) | |
Alcohol consumption | b | [27]: multi-cohort study, n = 16,245 individuals [33]: n = 1944 subjects drinking less than 1 versus n = 579 subjects drinking more than 3 drinks/week | ↓ with moderate alcohol consumption ↑ (up to 2.2 years) with habitual alcohol consumption / dependence / alcohol use disorder | ||
Smoking | [52]: 8 CpG-clock b | b, bc | [27]: multi-cohort study, n = 16,245 individuals [53]: n = 692 males; 66% former, 30% never, 4% current smokers | Inconsistent; trend ↑ | |
Exposure to environmental toxins | [55]: Levine (513 CpGs) p, 239 CpG-clock c | b, bu | [55]: 3 panels of Chinese populations, n = 539 [56]: longitudinal study; n = 589 males [57]: longitudinal study; n = 552 [58]: n = 1000 [59]: longitudinal study; n = 2747 women | Mainly ↑ (up to 6 years) | |
Sex | b, s | [3]: n = 656 subjects, 19–101 years old [28]: n = 238 males versus 232 females (middle-aged) [32]: n = 1918 males versus 3083 females | ↑ in males (~ 1 year) | ||
Ethnicity | [9]: 5 CpGs (ELOVL2, C1orf132, TRIM59, KLF14, FHL2) c [28]: Hannum (71 CpGs) c [29]: Levine (513 CpGs)p | b,s | EA differs between ethnicities (e.g. Hispanics and Tsimane Amerindians > Caucasians, African Americans < Caucasians and Hispanics) |
Factor | Reference | Age prediction model (referring to chronological (c), phenotypic (p) age) | K | Information on investigated populations (as far as available) | Influence on the estimation of chronological age |
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Insomnia | [64] | Horvath (353 CpGs)c, enhanced Hannum model (71 CpGs + blood cell counts)c | b | n = 411 women with versus n = 1667 without insomnia symptoms | ↑ (up to 1.77 years) |
Night shift work | [65] | Horvath (353 CpGs)c, Hannum (71 CpGs)c, Levine (513 CpGs)p | b | n = 175 (have been) working nightshift, n = 2399 never worked nights shift (women aged 35–74 years) | ↑ (~ 3 years) |
Parental depression at child age 11 | [66] | Horvath (353 CpGs)c | b mn | n = 242 11-year-old children with versus n = 157 without intervention | ↑ (at child age 20) |
Early onset Alzheimer’s disease | [11] | 5 CpGs (ELOVL2, C1orf132, KLF14, FHL2, TRIM59)c | b | n = 31 early onset Alzheimer’s disease patients (aged 31–44 years) versus n = 120 healthy controls | ↑ (mean 6.5 years) |
Graves’ disease | n = 44 Graves’ disease patients (aged 12–30 years) versus n = 120 healthy controls | ↑ (mean 3.7 years) | |||
Parkinson’s disease | [67] | 5 CpGs (ELOVL2, C1orf132, KLF14, FHL2, TRIM59)c Horvath (353 CpGs)c | b | n = 335 with versus n = 257 without Parkinson’s disease (35–92 years old) | ↑ |
Hutchinson Gilford progeria syndrome | [68] | Horvath skin and blood clock (391 CpGs)c | b | n = 14* Hutchinson Gilford progeria patients | ↑ |
Sotos, Rett and Kabuki syndrome | [69] | Horvath (353 CpGs) c | b | Sotos syndrome: n = 20* Rett syndrome: n = 15* Kabuki syndrome: n = 46* Healthy: n = 1128 | Sotos: ↑ (7.6 years) Rett: ↑ (2.7 years) Kabuki: ↓ (1.8 years) |
Nutrition | [33] | Horvath (353 CpGs)c Horvath (353 CpGs)c, Hannum (71 CpGs)c | b | n = 704 women with low versus n = 1156 with high fish consumption; n = 518 women with high versus n = 579 with low blood carotenoid levels; n = 748 women with high vs n = 826 with low poultry consumption | ↓ healthy (high carotenoids, fish) (up to 3.3 years) ↑ high poultry consumption |
Longevity of parents | [70] | Horvath (353 CpGs)c | b mn | n = 63* semi-supercentenarians’ offspring versus n = 47 controls | ↓ offspring (5.1 years) |
Intense physical exercise | [10] | 5 CpG clock (ELOVL2, C1orf132, KLF14, FHL2, TRIM59) c, 2CpG-clock (TRIM599, KLF14) c | b | n = 176 athletes versus n = 128 age- and gender-matched controls | ↑ (up to 5.9 years) |
Abnormal glucose tolerance during pregnancy | [71] | Hannum (71 CpGs) c, Levine (513 CpGs) p | b | n = 113 women with abnormal versus n = 2243 women with normal glucose tolerance during pregnancy | ↑ (mother) |