Selected Contribution: Bone adaptation with aging and long-term caloric restriction in Fischer 344 × Brown-Norway F1-hybrid rats

Abstract

Rodents are commonly used as models for human aging because of their relatively short life span, the ease of obtaining age-specific tissue samples, and lower cost. However, age-associated disease may confound inbred animal studies. For example, numerous physiologically significant lesions, such as chronic nephropathy, are more common in aged Fischer 344 (F344) rats than in other strains (Bronson RT, Genetic Effects of Aging, 1990). Conversely, F344 x Brown-Norway F1-hybrid (F344BN) rats, developed by the National Institute on Aging for aging research, live considerably longer and have fewer pathologies at any given age vs. inbred strains (Lipman RD, Chrisp CE, Hazzard DG, and Bronson RT, J Gerontol A Biol Sci Med Sci 51: 54-59, 1996). To our knowledge, there are no data regarding the effect of age on bone geometry and mechanics in this strain of rat. Furthermore, caloric restriction (CR) extends the mean and maximal life span of animals and significantly reduces age-associated disease but may have adverse consequences for bone growth and mechanics. Thus we investigated the effects of age and CR on bone geometry and mechanics in the axial and appendicular skeleton of F344 Brown-Norway rats. Ad libitum fed rats were assessed at 8 mo (young adult; n = 6), 28 mo (late middle age; n = 5), and 36 mo (senescence; n = 6). CR rats were assessed at 28 mo (n = 6). Tibiae and the sixth lumbar vertebrae (L6) were dissected, scanned (micro-computed tomography) to determine geometry, and tested mechanically. From 8 to 36 mo, there were no significant changes in L6 geometry, and only the cross-sectional moment of inertia changed (increased) with the tibia. CR-induced body mass reductions accounted for changes in L6 load at proportional limit, maximal load, and stiffness (structural properties), but altered tibial structural properties were independent of body mass. In tibiae, geometric changes dominated alterations in structural properties. Those data demonstrated that, whereas aging in ad libitum-fed animals induced minor changes in bone mechanics, axial and appendicular bones were adversely influenced by CR in late-middle-aged animals in different manners.

Bone quality is affected by food restriction and by nutrition-induced catch-up growth

“…Caloric restriction was shown to be associated with bone loss in middle-aged humans (Villareal et al 2006) and late-middle-aged rodents (LaMothe et al 2003); however, no changes in BMD were observed in this study, maybe due to the differences in age.…”

“…In recent years, the effect of RES on bone quality was assessed in several studies using micro-CT scanning and mechanical testing. However, most of these studies were carried out on adult animals and used diverse protocols, including different species (mostly mice and rats) of various ages, sex and strains, different extent, and duration of the restriction (from 4 weeks to 4 months) with matched or non-matched intake of micronutrients (Talbott et al 2001, LaMothe et al 2003, Lambert et al 2005. These variations make it quite difficult to make valid comparisons.…”

Effects of early-stage aging on locomotor dynamics and hindlimb muscle force production in the rat

“…Significant signs of sarcopenia in the Fischer 344 ϫ Brown Norway rats do not fully manifest until 33months of age (Lushaj et al, 2008). Although these rats reach skeletal maturity at ~6months, they increase in body mass in the form of adipose and connective tissues until ~30months of age, similar to the human trajectory (LaMothe et al, 2003;Lushaj et al, 2008;Turturro et al, 1999). Individuals were housed separately in standard laboratory rat cages in a temperature-regulated room (22-23°C) on a 12h:12h light:dark cycle and were provided with food and water ad libitum.…”

High-fat, sucrose diet impairs geometrical and mechanical properties of cortical bone in mice

“…Tibial geometry permits more stable and repeatable placement of the diaphyseal shaft on the loading span than the femoral diaphysis, which is more circular in cross section (23) . On the day of mechanical testing, tibiae were thawed in 228C PBS for at least 1 h. Tibial length was measured (^0·01 mm) using digital callipers (Model 14-648-17, Fisher Scientific, Ottawa, ON, Canada).…”