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. 2021 May;20(5):e13328.
doi: 10.1111/acel.13328. Epub 2021 Mar 31.

17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

David E Harrison  1 , Randy Strong  2   3   4   5 , Peter Reifsnyder  1 , Navasuja Kumar  6 , Elizabeth Fernandez  2   3   5 , Kevin Flurkey  1 , Martin A Javors  7 , Marisa Lopez-Cruzan  7 , Francesca Macchiarini  8 , James F Nelson  2   9 , Adrian Markewych  10 , Alessandro Bitto  10 , Amy L Sindler  11 , Gino Cortopassi  12 , Kylie Kavanagh  13 , Lin Leng  14 , Richard Bucala  14 , Nadia Rosenthal  1 , Adam Salmon  2   3   4   15 , Timothy M Stearns  1 , Molly Bogue  1 , Richard A Miller  6
Affiliations

17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

David E Harrison et al. Aging Cell. 2021 May.

Erratum in

Abstract

In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the "non-feminizing" estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p < 0.0001, log-rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang-Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex-specific aspects of aging.

Keywords: 17-α-estradiol; candesartan cilexetil; geranylgeranylacetone; heterogeneous mice; lifespan; macrophage migration inhibitory factor; nicotinamide riboside.

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Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
Effects of 17aE2 on lifespan curves showing male control and males fed 17aE2 diets started at 16 months or at 20 months of age. Table 1 gives more details on these lifespans
FIGURE 2
FIGURE 2
Effects of interventions on body weights. Panel A shows females, and Panel B shows males. Weights are from the same mice whose lifespans are shown in Table 1. Control mice were fed the control diet; 17aE2 started at 16 or 20 months of age. CC, MIF098, and NR were fed from 8 months of age, while GGA was fed from 9 months of age
FIGURE 3
FIGURE 3
Lifespan curves of controls, and the 4 interventions without effects/. Panel A shows females, and Panel B shows males. Data are from the same mice whose lifespans are shown in Table 1
FIGURE 4
FIGURE 4
Effects of site on control lifespans in this cohort. Panel A shows females, and Panel B shows males. p values are for median lifespans; controls did not differ significantly among the sites
See this image and copyright information in PMC

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