Figure and Table Outline


SLAM Study Numbers

Study Population

- Timeframe for current analysis: (12/9/2015 - 11/21/2018)
- n(1241): wave 1-6
  - Sex (Female): 50.20%
  - Strain (B6): 50.04%
  - Sex_Strain
    - Female_B6: 24.98%
    - Female_HET3: 25.22%
    - Male_B6: 25.06%
    - Male_HET#: 24.74%
      

Measurement Frequencies (mean (SD)

- Fasting blood glucose: 6.37 (2.45)
- Body weight: 46.49 (19.63)
- Body fat: 7.94 (3.38)

Death and Life Expectancy (median (IQR))

- Deaths (776)
- Median Life expectancy: 115.00 (98.00, 129.00)
  - Midlife or 50% MLE: 57.50 
  - Late Life or 75% MLE: 86.25 
  - Oldest in Life or 90% MLE: 103.50 

Rate of Change Increment (5% MLE)

- All: 6 weeks
- Female: 6 weeks
- Male: 6 weeks
- B6: 6 weeks
- HET3: 6 weeks
- Female_B6: 6 weeks
- Female_HET3: 6 weeks
- Male_B6: 6 weeks
- Male_HET3: 6 weeks

NHP Study Numbers

Study Population

- Timeframe for current analysis: 
- n: 254
  - Sex (Female): 43.70%
  - Cohort (NIA): 85.04%
  - Sex_Cohort
    - Female_NIA: 37.80%
    - Female_WIS: 5.91%
    - Male_NIA: 47.24%
    - Male_WIS: 9.06%
  - Diabetes: 3.54%
      

Measurement Frequencies (mean (SD)

- Fasting blood glucose: 18.61 (21.08)
- Body weight: 7.18 (11.16)
- Body fat: 7.18 (11.16)

Death and Life Expectancy (median (IQR))

- Deaths (87)
- Median Life expectancy: 26.74 (23.09, 30.30)
  - Midlife or 50% MLE: 13.37 
  - Late Life or 75% MLE: 20.06 
  - Oldest in Life or 90% MLE: 24.07 

Rate of Change Increment (5% MLE)

- All: 1 years
- Female: 1 years
- Male: 1 years
- NIA: 1 years
- WIS: 1 years
- Female_NIA: 1 years
- Female_WIS: 1 years
- Male_NIA: 1 years
- Male_WIS: 1 years

BLSA Study Numbers

Study Population

- Timeframe for current analysis: 
- n: 3023
  - Sex (Female): 46.64%
  - Race (Non-White): 22.36%
  - Diabetes: 15.15%
      

Measurement Frequencies (mean (SD)

- Fasting blood glucose: 5.83 (4.53)
- Body weight: 6.12 (4.76)
- Body fat: 5.77 (4.50)

Death and Life Expectancy (median (IQR))

- Deaths (1193)
- Median Life expectancy: 86.00 (79.00, 91.00)
  - Midlife or 50% MLE: 43.00 
  - Late Life or 75% MLE: 64.50 
  - Oldest in Life or 90% MLE: 77.40 

Rate of Change Increment (5% MLE)

- All: 4 years
- Female: 4 years
- Male: 4 years
- NW: 4 years
- W: 4 years

Overall Survival by Species Note: Dotted line represents median survival

Study Survival Characteristics
Metric Mice (SLAM) Nonhuman Primates Humans (BLSA)
N Total 1241 254 3023
N Dead 776 87 1193
Median Life Expectancy (IQR) 115.00 (98.00, 129.00) 26.74 (23.09, 30.30) 86.00 (79.00, 91.00)
Maximum Life Expectancy 181 42.03 109
Midlife 57.50 13.37 43.00
Late Life 86.25 20.06 64.50
Oldest in Life 103.50 24.07 77.40
Note:
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA); Median Life Expectancy (MLE), Interquartile Range (IQR)
Life expectancy values are in weeks for mice, and years for nonhuman primates and humans.

Overall Survival by Species and Subgroup Note: Dotted line represents median survival

Study Survival Characteristics by Subgroup
Mice (SLAM)
Nonhuman Primates
Humans (BLSA)
Metric Female B6 Female HET3 Male B6 Male HET3 Female NIA Female WIS Male NIA Male WIS Female Male
N Total 310 313 311 307 96 15 120 23 1410 1613
N Dead 210 180 195 191 22 15 28 22 408 785
Median Life Expectancy (IQR) 114.00 ( 98.00, 126.00) 117.00 ( 99.00, 131.00) 116.00 (102.00, 127.00) 113.00 ( 94.00, 129.00) 24.47 (20.97, 27.80) 23.86 (21.40, 27.55) 31.38 (27.74, 34.27) 26.30 (24.61, 28.93) 87.00 (80.00, 93.00) 85.00 (78.00, 90.00)
Maximum Life Expectancy 180 181 180 180 42.03 34.82 41.21 30.48 109 103
Midlife 57.00 58.50 58.00 56.50 12.23 11.93 15.69 13.15 43.50 42.50
Late Life 85.50 87.75 87.00 84.75 18.35 17.90 23.54 19.73 65.25 63.75
Oldest in Life 102.60 105.30 104.40 101.70 22.02 21.47 28.24 23.67 78.30 76.50
Note:
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA); Median Life Expectancy (MLE), Interquartile Range (IQR)
Life expectancy values are in weeks for mice, and years for nonhuman primates and humans.

Table S2: Correlation Coefficients of Metabolic Indices by Species
Mouse (SLAM)
Nonhuman Primates
Humans (BLSA)
Timepoint Glucose
x
Body Weight
Body Weight
x
Body Fat
Body Fat
x
Glucose
Glucose
x
Body Weight
Body Weight
x
Body Fat
Body Fat
x
Glucose
Glucose
x
Body Weight
Body Weight
x
Body Fat
Body Fat
x
Glucose
Midlife 0.52
(0.47, 0.56)*
0.91
(0.90, 0.92)*
0.48
(0.43, 0.53)*
0.33
(0.10, 0.52)*
0.88
(0.81, 0.92)*
0.34
(0.12, 0.54)*
0.30
(0.23, 0.38)*
0.91
(0.90, 0.93)*
0.32
(0.25, 0.40)*
Late Life 0.47
(0.42, 0.52)*
0.89
(0.88, 0.90)*
0.45
(0.40, 0.50)*
0.33
(0.12, 0.52)*
0.88
(0.81, 0.92)*
0.35
(0.14, 0.54)*
0.25
(0.19, 0.30)*
0.89
(0.88, 0.91)*
0.29
(0.23, 0.34)*
Oldest in Life 0.40
(0.34, 0.46)*
0.84
(0.82, 0.86)*
0.39
(0.33, 0.45)*
0.22
(-0.02, 0.43)
0.88
(0.82, 0.93)*
0.21
(-0.03, 0.43)
0.27
(0.21, 0.32)*
0.88
(0.87, 0.90)*
0.28
(0.22, 0.34)*
Note:
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA).
The numbers in parentheses are 95% CI.
p-value < 0.05 was considered statistically significant.

Trends in Metabolic Indices over the Lifespan across Species by Subgroup

  • Diamonds represent age at peak index value between 25% and 125% of median life expectancy
    • Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA).

Trends in Metabolic Indices over the Lifespan across Species by Subgroup (Lines Only)

  • Diamonds represent age at peak index value between 25% and 125% of median life expectancy
    • Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA).


Trends in Metabolic Indices over the Lifespan across Species by Diabetes Status


Trends in Metabolic Indices over the Lifespan Compared to External Studies


Rate of Percent Change in Metabolic Indices During Pre- and Post-Peak Phases across Species by Subgroup
Mice (SLAM)
Nonhuman Primates
Humans (BLSA)
Metabolic
Index
Subgroup Peak Age \(^†\)
(weeks)
Pre-Peak\(^‡\)\(^§\)Rate
(per 6 weeks)
Post-Peak\(^‡\)\(^§\)Rate
(per 6 weeks)
Subgroup Peak Age \(^†\)
(years)
Pre-Peak \(^‡\)\(^§\)Rate
(per year)
Post-Peak\(^‡\)\(^§\)Rate
(per year)
Subgroup Peak Age \(^†\)
(years)
Pre-Peak\(^‡\)\(^§\)Rate
(per 4 years)
Post-Peak\(^‡\)\(^§\)Rate
(per 4 years)
Gluose All 78.29
(67.43, 92.00)
0.11 %
(0.10, 0.13)*
-3.08 %
(-3.12, -3.04)*
All 26.89
(24.25, 31.25)
0.48 %
(0.47, 0.49)*
-0.68 %
(-0.71, -0.64)*
All 69.00
(63.00, 75.00)
0.70 %
(0.69, 0.70)*
-0.64 %
(-0.64, -0.63)*
Female B6 81.43
(67.43, 103.43)
1.02 %
(0.99, 1.05)*
-2.95 %
(-3.17, -2.74)*
Female NIA 26.08
(22.00, 30.58)
0.26 %
(0.24, 0.28)*
-0.64 %
(-0.70, -0.58)*
Female 69.00
(61.00, 76.00)
0.65 %
(0.65, 0.66)*
-0.58 %
(-0.58, -0.57)*
Female HET3 40.71
(35.00,92.00)
0.11 %
(0.11, 0.12)*
-1.02 %
(-1.07, -0.96)*
Female WIS 29.79
(18.46,29.82)
0.66 %
(0.48, 0.84)*
Peak at 125% MLE Male 67.00
(58.00, 75.00)
0.75 %
(0.74, 0.76)*
-0.57 %
(-0.58, -0.57)*
Male B6 76.43
(54.29, 92.00)
0.96 %
(0.94, 0.98)*
-4.38 %
(-4.45, -4.30)*
Male NIA 38.58
(29.25, 38.83)
0.23 %
(0.23, 0.23)*
Peak at 125% MLE
Male HET3 36.00
(36.00,63.43)
Peak at 25% MLE -1.89 %
(-1.96, -1.82)*
Male WIS 29.86
(22.96,30.44)
1.25 %
(1.16, 1.33)*
2.54 %
(2.54, 2.54)*
Body Weight All 77.43
(71.00, 84.14)
0.65 %
(0.65, 0.66)*
-0.67 %
(-0.67, -0.67)*
All 17.00
(13.50, 33.42)
0.28 %
(0.27, 0.29)*
-0.05 %
(-0.06, -0.05)*
All 60.00
(52.00, 66.00)
0.81 %
(0.80, 0.82)*
-1.35 %
(-1.36, -1.34)*
Female B6 85.14
(80.14, 91.00)
0.65 %
(0.65, 0.65)*
-0.61 %
(-0.61, -0.60)*
Female NIA 19.25
(14.50, 27.75)
0.11 %
(0.11, 0.11)*
-0.10 %
(-0.11, -0.09)*
Female 61.00
(54.00, 67.00)
1.03 %
(1.02, 1.03)*
-1.22 %
(-1.22, -1.21)*
Female HET3 84.14
(74.14, 94.14)
0.94 %
(0.93, 0.95)*
-0.81 %
(-0.82, -0.80)*
Female WIS 18.39
(8.72, 29.82)
0.15 %
(0.14, 0.16)*
-0.10 %
(-0.11, -0.09)*
Male 52.00
(44.00, 59.00)
0.96 %
(0.94, 0.98)*
-1.42 %
(-1.43, -1.41)*
Male B6 68.00
(60.14, 75.00)
0.70 %
(0.69, 0.71)*
-0.80 %
(-0.80, -0.79)*
Male NIA 16.58
(12.50, 21.50)
0.21 %
(0.20, 0.22)*
-0.03 %
(-0.04, -0.02)*
Male HET3 74.00
(66.14, 79.86)
0.78 %
(0.76, 0.79)*
-1.09 %
(-1.10, -1.08)*
Male WIS 16.52
(6.63, 30.44)
0.20 %
(0.19, 0.21)*
-0.19 %
(-0.20, -0.18)*
Body Fat All 71.14
(61.86, 83.86)
0.36 %
(0.35, 0.36)*
-0.36 %
(-0.37, -0.36)*
All 17.84
(15.50, 33.42)
0.17 %
(0.17, 0.18)*
-0.03 %
(-0.04, -0.03)*
All 73.00
(65.00, 80.00)
0.88 %
(0.87, 0.88)*
-0.55 %
(-0.56, -0.54)*
Female B6 88.14
(77.43, 95.29)
0.31 %
(0.31, 0.32)*
-0.41 %
(-0.43, -0.40)*
Female NIA 19.25
(15.75, 27.75)
0.11 %
(0.10, 0.12)*
-0.08 %
(-0.09, -0.08)*
Female 69.00
(61.00, 78.00)
1.00 %
(0.99, 1.01)*
-0.28 %
(-0.28, -0.28)*
Female HET3 81.86
(63.29, 100.14)
0.40 %
(0.38, 0.41)*
-0.48 %
(-0.50, -0.46)*
Female WIS 18.11
(8.72, 29.82)
0.14 %
(0.13, 0.15)*
-0.04 %
(-0.04, -0.04)*
Male 68.00
(57.00, 78.00)
1.01 %
(0.99, 1.03)*
-0.36 %
(-0.36, -0.35)*
Male B6 66.14
(57.43, 77.00)
0.35 %
(0.34, 0.36)*
-0.43 %
(-0.43, -0.42)*
Male NIA 29.08
(23.58, 33.50)
0.04 %
(0.03, 0.04)*
-0.20 %
(-0.23, -0.18)*
Male HET3 67.00
(54.43, 80.14)
0.44 %
(0.42, 0.45)*
-0.50 %
(-0.51, -0.49)*
Male WIS 21.22
(6.63, 30.44)
0.10 %
(0.09, 0.11)*
-0.09 %
(-0.10, -0.09)*
Note:
Entire population and subgroup-specific values are both listed.
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA).
One sample Student’s t-test was used to test whether the means are significantly different from zero.
p-value < 0.05 was considered statistically significant.
Mean (range of ages at similar values) of age at peak index value
Mean (95% confidence interval) rate of percent change
§ Pre-peak is defined as 25% life expectancy to age at peak value; post-peak is defined as peak to 125% life expectancy

Kaplan-Meier Survival Curve and Age-adjusted Mortality Hazard Ratio Highest and Lowest Glucose Quartiles Varying Timepoints across Species

*p-value < 0.05 was considered statistically significant. Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA).

Survival Curve and Age Adjusted Mortality Hazard Ratio Comparing Highest and Lowest Body Weight Quartiles at Varying Timepoints across Species

Survival Curve and Age Adjusted Mortality Hazard Ratio Comparing Highest and Lowest Body Fat Quartiles at Varying Timepoints across Species


Test of Statistical Interaction of Mortality Hazard Ratio Comparing Highest and Lowest Metabolic Index Quartiles at Varying Timepoints by Sex and Strain/Cohort
Mice (SLAM)
Nonhuman Primates
Humans (BLSA)
Metabolic
Index
Time Point Sex Strain Sex Cohort Sex Race
Glucose Midlife 0.10 0.72 0.08 0.98 0.22 0.13
Late Life 0.42 0.16 0.69 0.21 0.96 0.73
Oldest in Life 0.23 0.47 0.18 0.07 0.91 0.38
Body Weight Midlife 0.08 0.96 0.38 0.65 0.35 0.27
Late Life 0.22 0.94 0.98 0.51 0.33 0.85
Oldest in Life 0.14 0.25 0.31 0.24 0.28 0.36
Body Fat Midlife 0.22 0.52 0.39 0.47 0.71 0.81
Late Life 0.12 0.60 0.36 0.15 0.22 1.00
Oldest in Life 0.76 0.02 0.53 0.17 1.00 0.63
Note:
P-values are calculated from a likelihood ratio test comparing the base model of age,
sex, and strain, with a model additionally adjusting for the interaction term.


Mice (SLAM)
Nonhuman Primates
Humans (BLSA)
Group Timepoint\(^†\) HR\(^1\) HR\(^2\) HR\(^1\) HR\(^2\) HR\(^1\) HR\(^2\)
All Midlife 1.05 (0.85, 1.29) 1.02 (0.82, 1.28) 0.88 (0.43, 1.80) 0.46 (0.21, 0.97)* 1.60 (0.75, 3.42) 1.42 (0.64, 3.15)
Late Life 0.97 (0.78, 1.20) 1.09 (0.87, 1.38) 2.50 (1.15, 5.46)* 1.82 (0.71, 4.65) 1.40 (1.05, 1.86)* 1.36 (1.00, 1.83)*
Oldest in Life 0.76 (0.59, 0.97)* 0.96 (0.74, 1.25) 3.00 (1.34, 6.70)* 2.32 (0.87, 6.17) 1.32 (1.06, 1.65)* 1.09 (0.76, 1.58)
Female Midlife 1.04 (0.78, 1.40) 1.06 (0.78, 1.45) 0.31 (0.09, 1.08) 0.23 (0.07, 0.83)* 1.11 (0.38, 3.26) 0.99 (0.33, 3.00)
Late Life 0.95 (0.69, 1.29) 1.08 (0.78, 1.50) 0.99 (0.27, 3.65) 1.44 (0.29, 7.08) 1.24 (0.76, 2.02) 1.45 (0.86, 2.42)
Oldest in Life 0.63 (0.44, 0.90)* 0.74 (0.51, 1.08) 1.68 (0.50, 5.63) 1.03 (0.28, 3.80) 1.40 (0.95, 2.05) 1.40 (0.95, 2.08)
Male Midlife 1.05 (0.79, 1.41) 0.98 (0.71, 1.34) 1.62 (0.61, 4.30) 0.70 (0.24, 2.02) 1.84 (0.62, 5.42) 1.56 (0.50, 4.87)
Late Life 1.01 (0.74, 1.37) 1.09 (0.79, 1.52) 4.21 (1.42, 12.48)* 2.26 (0.64, 7.93) 1.39 (0.98, 1.97) 1.26 (0.87, 1.82)
Oldest in Life 0.90 (0.64, 1.26) 1.31 (0.90, 1.92) 12.79 (3.43, 47.72)* 10.67 (2.61, 43.65)* 1.29 (0.98, 1.70) 1.28 (0.96, 1.71)
Note:
Entire population and subgroup-specific values are both listed.
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA)
The numbers in parentheses are 95% CI.
* p-value < 0.05 was considered statistically significant.
Midlife: 50% median life expectancy, late-life: 75% median life expectancy, oldest in life: 90% median life expectancy.
Hazard ratios are adjusted for: 1) age and sex; 2) additionally adjusted for body fat.

Mortality Hazard Ratios of Highest and Lowest Body Weight and Body Fat Quartiles at Varying Timepoints across Species by Subgroup

Metabolic Index Group Timepoint\(^†\) Mice
(SLAM)
Nonhuman
Primates
Humans
(BLSA)
Body Weight All Midlife 1.04 (0.85, 1.27) 2.05 (1.01, 4.17)* 1.33 (0.67, 2.61)
Late Life 0.78 (0.63, 0.97)* 1.81 (0.89, 3.69) 1.27 (0.94, 1.72)
Oldest in Life 0.60 (0.47, 0.77)* 1.82 (0.87, 3.82) 1.06 (0.85, 1.31)
Female Midlife 0.87 (0.65, 1.16) 1.63 (0.46, 5.83) 1.83 (0.63, 5.30)
Late Life 0.77 (0.57, 1.06) 2.32 (0.67, 8.09) 0.70 (0.40, 1.25)
Oldest in Life 0.72 (0.51, 1.02) 1.57 (0.49, 5.09) 1.04 (0.72, 1.50)
Male Midlife 1.24 (0.93, 1.66) 2.44 (1.00, 5.98) 1.15 (0.47, 2.80)
Late Life 0.79 (0.58, 1.06) 1.75 (0.66, 4.65) 1.54 (1.07, 2.21)*
Oldest in Life 0.48 (0.34, 0.67)* 2.93 (0.96, 8.95) 1.05 (0.80, 1.38)
Body Fat All Midlife 1.08 (0.89, 1.32) 2.10 (1.05, 4.21)* 1.46 (0.68, 3.12)
Late Life 0.76 (0.61, 0.94)* 1.72 (0.79, 3.73) 0.97 (0.72, 1.30)
Oldest in Life 0.52 (0.41, 0.67)* 2.26 (1.05, 4.85)* 0.91 (0.72, 1.14)
Female Midlife 0.91 (0.69, 1.21) 2.18 (0.62, 7.65) 1.55 (0.52, 4.65)
Late Life 0.68 (0.50, 0.93)* 1.46 (0.44, 4.89) 0.63 (0.37, 1.09)
Oldest in Life 0.59 (0.42, 0.84)* 1.97 (0.62, 6.21) 0.79 (0.54, 1.16)
Male Midlife 1.29 (0.97, 1.71) 2.15 (0.85, 5.42) 1.42 (0.49, 4.13)
Late Life 0.88 (0.66, 1.19) 2.48 (0.76, 8.11) 1.12 (0.79, 1.59)
Oldest in Life 0.44 (0.32, 0.62)* 2.43 (0.85, 6.95) 0.96 (0.72, 1.27)
Note:
Abbreviations: Study of Longitudinal Aging in Mice (SLAM); Baltimore Longitudinal Study of Aging (BLSA)
* p-value < 0.05 was considered statistically significant.
Midlife: 50% median life expectancy, late-life: 75% median life expectancy, oldest in life: 90% median life expectancy
Hazard ratios (95% confidence intervals) are adjusted for age, sex, and strain/cohort