SummaryTo better characterize aging in mice, the Jackson Aging Center carried out a lifespan study of 31 geneticallydiverse 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 insulinlike 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 shortlived 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.

WOOLEY, C.M., S. XING, R.W. BURGESS, G.A. COX, AND K.L. SEBURN. Age, experience and genetic background influence treadmill walking in mice. PHYSIOL. BEHAV. XX(X), XXX-XXX, 2008 -The use of a treadmill to gather data for gait analysis in mice is a convenient, sensitive method to evaluate motor performance. However, evidence from several species, including mice, shows that treadmill locomotion is a novel task that is not equivalent to over ground locomotion and that may be particularly sensitive to the test environment and protocol. We investigated the effects of age, genetic background and repeated trials on treadmill walking in mice and show that these factors are important considerations in the interpretation of gait data. Specifically we report that as C57BL/6J (B6) mice age, the animals use progressively longer, less frequent strides to maintain the same walking speed. The increase is most rapid between 1 and 6 months of age and is explained, in part, by changes in size and weight. We also extended previous findings showing that repeat trials cause mice to modify their treadmill gait pattern. In general, B6 mice tend to take shorter, more frequent steps and adopt a wider dynamic stance with repeated walking trials. The nature and extent of the response changes with both the number and timing of the trials and was observed with intertrial intervals as long as 3 months. Finally, we compared the gait pattern of an additional seven inbred strains of mice and found significant variation in the length and frequency of strides used to maintain the same walking speed. The combined results offer the bases for further mechanistic studies and can be used to guide optimal experimental design.

Understanding the genetic influence on ECG time intervals and heart rate (HR) is important for identifying the genes underlying susceptibility to cardiac arrhythmias. The objective of this study was to determine the genetic influence on ECG parameters and their age-related changes in mice. ECGs were recorded in lead I on 8 males and 8 females from each of 28 inbred strains at the ages of 6, 12, and 18 mo. Significant interstrain differences in the P-R interval, QRS complex duration, and HR were found. Age-related changes in the P-R interval, QRS complex duration, and HR differed among strains. The P-R interval increased with age in 129S1/SvlmJ females. The QRS complex duration decreased with age in C57BR/J males and DBA2/J females but increased in NON/ShiLtJ females. HR decreased in C57L/J females and SM/J and P/J males but increased in BALB/cByJ males. Differences between males and females were found for HR in SJL/J mice and in the P-R interval in 129S1/SvlmJ mice. Broad-sense heritability estimates of ECG time intervals and HR ranged from 0.31 for the QRS complex duration to 0.52 for the P-R interval. Heritability estimates decreased with age for the P-R interval. Our study revealed that genetic factors play a significant role on cardiac conduction activity and age-related changes in ECG time intervals and HR.

Blood lead concentrations are higher in young children than in other age groups, whereas little is known regarding concentrations of other metals in young children. We measured the concentrations of a suite of metals in the blood of children 1-6 years of age, and assessed potential differences by age, season, or region of Maine. We used blood submitted to the Maine State Health and Environmental Testing Laboratory for blood lead analysis to determine the concentrations of arsenic (As), antimony (Sb), cadmium (Cd), manganese (Mn), mercury (Hg), selenium (Se), tin (Sn), and uranium (U) in 1350 children 1-6 years of age. The essential metals Mn and Se were detected in all samples, and As and Sb were detected in 490% of samples. Hg was detected in approximately 60% of samples. U and Cd were less often detected in blood samples, at approximately 30% and 10% of samples, respectively. Sn was not detected in any sample. Concentrations of As, Hg, and Se increased with age, whereas Sb decreased with age. Concentrations also varied by season and region for some though not all metals. Significant pairwise correlations were observed for a number of metals. Blood is a reasonable compartment for measurement of most of these metals in young children. The use of convenience samples provided a cost-effective mechanism for assessing exposure of young children in Maine.