Table 2.

Relationships of Mission Duration with Aging Biomarkers and Leukocyte Proportions

	Difference in DNA Methylation Marker (95% CI) Aging Biomarker Model^a	p^b
DNAmGrimAge (Years)
Baseline (−7 days)	reference	ND
60 days	−0.52 (−2.72 to 1.67)	0.65
168 days	−4.50 (−6.79 to 2.20)	0.001
300 days	−2.12 (−4.41 to 0.17)	0.09
512 days	0.38 (−2.35 to 3.10)	0.79
Post-mission (527 days)	0.06 (−2.35 to 2.47)	0.96
DNAmPhenoAge (Years)
Baseline (−7 days)	reference	ND
60 days	−2.39 (−5.38 to 0.61)	0.11
168 days	−5.90 (−9.03 to −2.77)	0.001
300 days	−4.14 (−7.27 to −1.02)	0.01
512 days	−3.04 (−6.76 to 0.68)	0.10
Post-mission (527 days)	−5.41 (−8.70 to −2.12)	0.003
DNAmTL (kb)
Baseline (−7 days)	reference	ND
60 days	0.03 (−0.07 to 0.14)	0.48
168 days	0.02 (−0.08 to 0.12)	0.67
300 days	0.02 (−0.09 to 0.13)	0.70
512 days	0.03 (−0.08 to 0.14)	0.58
Post-mission (527 days)	−0.01 (−0.11 to 0.08)	0.76
Pace of Aging (PoA) (Years)
Baseline (−7 days)	reference	ND
60 days	0.03 (−0.02 to 0.09)	0.19
168 days	0.01 (−0.04 to 0.07)	0.60
300 days	−0.01 (−0.07 to 0.05)	0.65
512 days	0.04 (−0.02 to 0.10)	0.15
Post-mission (527 days)	0.002 (−0.05 to 0.05)	0.94
Mitotic Age (epiTOC2) (Divisions per Stem Cell per Year)
Baseline (−7 days)	reference	ND
60 days	−397.21 (−710.69 to −83.73)	0.02
168 days	−481.53 (−806.91 to −156.16)	0.006
300 days	−137.62 (−463.80 to 188.56)	0.39
512 days	−313.55 (−698.51 to 71.40)	0.10
Post-mission (527 days)	−216.67 (−557.20 to 123.87)	0.20
DNAmGrimAge Component Model^a
DNAm ADM (pg/mL)
Baseline (−7 days)	reference	ND
60 days	−9.21 (−18.72 to 0.31)	0.07
168 days	−22.66 (−32.60 to −12.72)	0.0003
300 days	−12.02 (−21.95 to −2.08)	0.03
512 days	−0.62 (−12.44 to 11.19)	0.92
Post-mission (527 days)	−2.53 (−12.99 to 7.93)	0.64
DNAm B2M (pg/mL)
Baseline (−7 days)	reference	ND
60 days	−11,537.7 (−54,851.00 to 31,775.68)	0.58
168 days	−46,459.3 (−90,099.30 to −28,19.31)	0.04
300 days	−42,559.8 (−87,307.27 to 2,187.72)	0.06
512 days	17,348.3 (−31,813.55 to 66,510.23)	0.47
Post-mission (527 days)	21,684.3 (21,852.57 to 65,221.21)	0.31
DNAm Cystatin C (pg/mL)
Baseline (−7 days)	reference	ND
60 days	8,025.9 (−11,508.78 to 27,560.51)	0.40
168 days	−4,456.8 (−24,120.16 to 15,206.56)	0.64
300 days	−5,041.1 (−25,701.20 to 15,619.04)	0.61
512 days	−5,248.7 (−26,859.24 to 16,361.76)	0.62
Post-mission (527 days)	7,124.1 (−12,024.12 to 26,272.35)	0.44
DNAm GDF-15 (pg/mL)
Baseline (−7 days)	reference	ND
60 days	−36.51 (−103.14 to 30.12)	0.26
168 days	−96.62 (−164.04 to −29.20)	0.008
300 days	−39.12 (−111.96 to 33.71)	0.27
512 days	10.92 (−61.50 to 83.35)	0.76
Post-mission (527 days)	−19.67 (−83.85 to 44.51)	0.53
DNAm Leptin (pg/mL)
Baseline (−7 days)	reference	ND
60 days	1,225.78 (−57.88 to 2,509.45)	0.06
168 days	−168.65 (−1,463.03 to 1,125.73)	0.79
300 days	188.22 (−1,135.56 to 1,512.00)	0.77
512 days	−306.50 (−1,769.60 to 1,156.60)	0.67
Post-mission (527 days)	360.37 (−935.18 to 1,655.92)	0.57
DNAm Packyears (Pack-Years)
Baseline (−7 days)	reference	ND
60 days	0.36 (−3.11 to 3.84)	0.83
168 days	0.14 (−3.40 to 3.67)	0.94
300 days	0.70 (−2.87 to 4.28)	0.68
512 days	1.21 (−2.87 to 5.29)	0.54
Post-mission (527 days)	0.77 (−2.84 to 4.38)	0.66
DNAm PAI-1 (pg/mL)
Baseline (−7 days)	reference	ND
60 days	1,160.27 (−383.77 to 2,704.31)	0.13
168 days	−1,364.61 (−2,920.97 to 191.75)	0.08
300 days	261.24 (−1,390.39 to 1,912.88)	0.74
512 days	−218.50 (−1,914.57 to 1,477.58)	0.79
Post-mission (527 days)	−132.06 (−1,635.02 to 1,370.91)	0.86
DNAm TIMP-1 (pg/mL)
Baseline (−7 days)	Reference	ND
60 days	−170.00 (−683.06 to 343.07)	0.50
168 days	−681.05 (−1,198.05 to−164.04)	0.01
300 days	−280.04 (−809.90 to 249.82)	0.28
512 days	71.26 (−511.54 to 654.06)	0.80
Post-mission (527 days)	57.91 (−458.20 to 574.01)	0.82
Leukocyte Model^c
B Cells
Baseline (−7 days)	reference	ND
60 days	−0.003 (−0.02 to 0.01)	0.65
168 days	−0.00005 (−0.02 to 0.01)	0.99
300 days	0.02 (0.001 to 0.03)	0.03
512 days	0.02 (0.002 to 0.03)	0.03
Post-mission (527 days)	−0.003 (−0.02 to 0.01)	0.73
CD4 Naive Cells
Baseline (−7 days)	reference
60 days	−53.30 (−111.04 to 4.44)	0.07
168 days	−84.27 (−142.01 to −26.54)	0.01
300 days	−11.06 (−68.80 to 46.67)	0.70
512 days	41.34 (−16.39 to 99.08)	0.15
Post-mission (527 days)	−36.39 (−94.12 to 21.35)	0.21
CD4 T Cells
Baseline (−7 days)	reference	ND
60 days	0.01 (−0.02 to 0.04)	0.54
168 days	0.001 (−0.03 to 0.03)	0.96
300 days	0.06 (0.03 to 0.09)	0.0008
512 days	0.05 (0.02 to 0.09)	0.003
Post-mission (527 days)	−0.001 (−0.03 to 0.03)	0.93
CD8 Naive Cells
Baseline (−7 days)	reference	ND
60 days	−20.67 (−40.00 to −1.36)	0.04
168 days	−8.23 (−27.55 to 11.09)	0.39
300 days	1.27 (−18.05 to 20.59)	0.89
512 days	37.95 (18.63 to 57.27)	0.0004
Post-mission (527 days)	1.13 (−18.19 to 20.45)	0.91
CD8pCD28nCD45Ran T Cells
Baseline (−7 days)	reference	ND
60 days	1.36 (−1.06 to 3.79)	0.26
168 days	1.76 (−0.67 to 4.18)	0.15
300 days	−1.39 (−3.81 to 1.03)	0.25
512 days	0.03 (−2.39 to 2.45)	0.98
Post-mission (527 days)	1.76 (−0.66 to 4.18)	0.15
CD8 T Cells
Baseline (−7 days)	reference	ND
60 days	−0.01 (−0.04 to 0.01)	0.31
168 days	−0.03 (−0.06 to −0.003)	0.03
300 days	−0.002 (−0.03 to 0.02)	0.86
512 days	0.02 (−0.007 to 0.05)	0.14
Post-mission (527 days)	−0.02 (−0.04 to 0.008)	0.17
Granulocytes
Baseline (−7 days)	reference	ND
60 days	0.01 (−0.04 to 0.06)	0.70
168 days	0.04 (−0.008 to 0.09)	0.10
300 days	0.0008 (−0.05 to 0.05)	0.98
512 days	−0.05 (−0.10 to 0.002)	0.06
Post-mission (527 days)	0.05 (0.0009 to 0.10)	0.05
Monocytes
Baseline (−7 days)	reference	ND
60 days	0.02 (0.002 to 0.03)	0.03
168 days	0.01 (−0.004 to 0.03)	0.15
300 days	−0.01 (−0.03 to 0.0002)	0.05
512 days	−0.01 (−0.02 to 0.007)	0.30
Post-mission (527 days)	0.002 (−0.01 to 0.02)	0.74
NK Cells
Baseline (−7 days)	reference	ND
60 days	−0.03 (−0.06 to −0.005)	0.02
168 days	−0.02 (−0.04 to 0.01)	0.29
300 days	−0.05 (−0.08 to −0.02)	0.002
512 days	−0.03 (−0.06 to −0.004)	0.03
Post-mission (527 days)	−0.04 (−0.07 to −0.007)	0.02
Plasmablasts
Baseline (−7 days)	reference	ND
60 days	−0.02 (−0.13 to 0.08)	0.64
168 days	0.03 (−0.07 to 0.14)	0.53
300 days	−0.17 (−0.27 to −0.06)	0.003
512 days	−0.17 (−0.28 to −0.07)	0.003
Post-mission (527 days)	−0.02 (−0.12 to 0.09)	0.71

Models adjusted for baseline DNAmAgeSkinBloodClock and white blood cell proportions.

Italicized p values are considered statistically significant in these analyses. ND, no data.

Models adjusted for baseline DNAmAgeSkinBloodClock.