Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels.
To better characterize aging in mice, the Jackson Aging Center carried out a lifespan study of 31 genetically-diverse inbred mouse strains housed in a specific pathogen-free facility. Clinical assessments were carried out every 6 months, measuring multiple age-related phenotypes including neuromuscular, kidney and heart function, body composition, bone density, hematology, hormonal levels, and immune system parameters. In a concurrent cross-sectional study of the same 31 strains at 6, 12, and 20 months, more invasive measurements were carried out followed by necropsy to assess apoptosis, DNA repair, chromosome fragility, and histopathology. In this report, which is the initial paper of a series, the study design, median lifespans, and circulating insulin-like growth factor 1 (IGF1) levels at 6, 12, and 18 months are described for the first cohort of 32 females and 32 males of each strain. Survival curves varied dramatically among strains with the median lifespans ranging from 251 to 964 days. Plasma IGF1 levels, which also varied considerably at each time point, showed an inverse correlation with a median lifespan at 6 months (R = -0.33, P = 0.01). This correlation became stronger if the short-lived strains with a median lifespan < 600 days were removed from the analysis (R = -0.53, P < 0.01). These results support the hypothesis that the IGF1 pathway plays a key role in regulating longevity in mice and indicates that common genetic mechanisms may exist for regulating IGF1 levels and lifespan.
Yuan
Rong
R
The Jackson Aging Center at The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Tsaih
Shirng-Wern
SW
Petkova
Stefka B
SB
Marin de Evsikova
Caralina
C
Xing
Shuqin
S
Marion
Michael A
MA
Bogue
Molly A
MA
Mills
Kevin D
KD
Peters
Luanne L
LL
Bult
Carol J
CJ
Rosen
Clifford J
CJ
Sundberg
John P
JP
Harrison
David E
DE
Churchill
Gary A
GA
Paigen
Beverly
B
D000818:Animals; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008136:Longevity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012107:Research Design; D016019:Survival Analysis
D007334:Insulin-Like Growth Factor I