Table 2 Studies investigating the association between the epigenetic clock and the incidence of age-related diseases

[69]

Cohort study

WHI

(USA)

2029, age 65.3 (7.1) 100% ♀

(post-menopause).

20 years FU

Lung cancer incidence; n = 43

Blood; 450 K

IEAAH

↑ risk of lung cancer (HR 1.50; p = 0.003), especially septuagenarians (HR:2.51, p = 0.0008) and current smokers (HR 6.17, p = 0.0004)

[NS]

Age, ethnicity, smoking, and pack years

[70]

Cohort study

NAS

(USA)

442, 71.7 (6.7), 0% ♀,

370 seen pre 2003,

306 in cohort 2003 to 2013.

3–5 years FU

Cancer incidence, n = 132

Buffy coat

(3 years FU); 450 K

IEAAHa

↑ cancer incidence (HR 1.06, p = 0.004 per year) in 2003–2013 cohort only

[NS]

Age, BMI, education, smoking, alcohol

[63]

Case-control

EPIC

(10 countries)

902 Total, 52.3 (8.9), 100% ♀

451 cases

451 CT

Breast cancer

Blood; 450 K

IEAAH

↑ breast cancer (4%, p = 0.016). In stratified analysis, only significant for postmenopausal ♀

[0.76]

BMI, hormonal factors, various others

[64]

Case-control

EPIC

(10 countries)

845 Total, 52 (7.4), 77.8% ♀

235 BC

166 CRC

Breast/colorectal cancer

Blood; 450 K

AAH

AAHa IEAAH

IEAAHa

In males, ↑ AAH in CRC (1.6 years older, p = 0.04)

NS all in females

[NS]

Cell %

[13]

Seven case-control studies nested in MCCS

Case-control

(Australia)

6432 total, 27–76, 59% ♀

3216 cancer cases**

3216 CT

Median 8.3 years FU

Cancer

Blood; 450 K

All

↑ cancer risk (7 of 35 associations, p < 0.05, mainly kidney ↑ 35–63% and B cell lymphomas ↑15–27%).

[EAH: r = 0.73, EAHa:0.78]

Age and sex, matched, various others

[23]

10 cohorts (∆ ethnicities) WHI, BHS, PEG (USA), cohorts from Bolivia, Asia, and Africa

Total 4296

(individual cohorts 41–1462),

2–92 (NS), between 0% and 100% ♀

Incident coronary heart disease (CHD), n = not stated

Blood

(3× saliva)

450 K

(2 × 27 K)

IEAAH

EEAA

NS

[EAH assumed: r = 0.65 to 0.93 depending on cohort, 3 of 10 > 0.80]

Age, sex, cell %, education

[62]

Cohort study

IS: BASICMAR

CT: REGICOR

(Spain)

IS: 82, 63.9 (10.3), 45.1% ♀

CT: 41, 62.8 (14.2), 48.8% ♀

Ischemic stroke

Whole blood; 450 K

AAH

AAHa

↑ stroke patients (AAHa: 2.5 years, p = 0.008; AAH NS), especially younger patients

[All samples, EAH: r = 0.87, EAHa:0.80]

Sex

[67]

Two cohorts of ischemic stroke (IS) patients (Spain)

Discovery:

551, 65–81 (NS), 41.9% ♀;

Replication:

85, 66–80 (NS), 29.4% ♀

IS outcome at 3 months (from 0 = no symptoms to 6 = death)

Whole blood; 450 K

AAHa

↑ worse 3-month stroke outcome (OR:1.04, p = 0.008 and OR 1.16, p < 0.001 in 2 cohorts).

[r = 0.81]

Age, sex, smoking, treatment, various others

[74]

Cohort study

PIVUS

(Sweden)

832, 70 (NS), 50% ♀

10years FU

Incident CVD, n = 153

Whole blood; 450 K

AAH

AAHa

↑ incident CVD (3.3% per year, p = 0.02) with AAH. AAHa NS

[NS]

Sex, smoking, BMI, various others

[16]

Case-control

PEG

(USA)

Caucasians:

289 PD, 37–91 (NS), 43% ♀;

219 CT, 35–92 (NS), 47% ♀.

Hispanics:

46 PD, 37–83 (NS), 30% ♀

38 CT, 35–92 (NS), 53% ♀

Parkinson’s disease (PD)

Blood; 450 k

AAH

IEAAH EEAA

Associated with PD after logistic regression (AAH: p = 0.037; EEAA p = 0.031. Effect sizes not stated.

[Caucasians: r = 0.82, Hispanics: r = 0.81]

Age, sex, cell %, smoking, ethnicity, coffee, pesticides

[68]

Cohort study

Betula

(Sweden)

16 maintain memory, 57.8 (3.6)

20 average, 58.0 (3.5)

16 decline, 57.9 (3.6), 50% ♀.

15 years FU

Dementia incidence, n = 7

Blood; 450 K

AAH

↑ dementia incidence (β 0.16, p = 0.03). [r = 0.69]

Age, sex