Growth negatively impacts the life span of mammals

Abstract

A negative intraspecific relationship between growth and longevity was proposed in the early 20th century. Indeed, stunting the growth of rodents by restricting their food dramatically extended life span. Subsequently, however, the hypothesis that growth exacerbates aging rates fell into disfavor. Contributing to this was (a) the establishment of a positive relationship between body size and longevity interspecifically, (b) purported antiaging impacts of growth hormone, and (c) the fact that the longevity of even mature rodents that had completed growth was extended by dietary restriction. Furthermore, intraspecific analytical studies failed to provide any clear resolution. This article presents the first global analyses of maximal longevity versus maximum mature mass for laboratory rats and mice, based on a relatively comprehensive compilation of research across the 20th century. Peak body mass (which reflects juvenile growth rates) was negatively associated with longevity within both species. Proximal mechanisms for impacts of growth on longevity appear congruent with the free radical and immunological theories of aging.

Hormonal regulation of longevity in mammals

“…Furthermore, the fact that small body size is strongly associated with longevity also holds true for domestic dogs (Patronek et al, 1997) and humans (Samaras et al, 2003). The relationship between small body size and longevity is further supported by reports showing that mice selected for reduced body sizes live longer (Eklund and Bradford, 1977;Roberts, 1961;Rollo, 2002;Miller et al, 2002) and calorie restriction also reduces growth and adult body size (Duffy et al, 1990). Therefore, growth negatively influences life span in mammals (Rollo, 2002) and likely other species.…”

“…However, disposing of glucose was reduced in both types of mice, indicating a decreased ability to increase insulin secretion in response to an acute glucose challenge. The heightened insulin responsiveness in these animals may be due to the elevated levels of liver insulin receptors (IR; protein) in GHR/BP KO mice and higher levels of IR, IRS-1 and IRS-2 (downstream effectors of the insulin receptor) in liver tissues of Ames mice 2002). This evidence is supported by decreased numbers of pancreatic islets in the Ames mouse (Parsons et al, 1995).…”

“…In addition, GH/IGF-I deficient mice develop significantly less osteoarthritis than wild-type mice (Silberberg, 1972). It has been postulated that stress resistance is coordinately increased (heat shock proteins, antioxidants, detoxification systems, metal chelators, and repair systems) and this up regulation results in multi-stress resistance to different stressors (Rollo, 2002;Jazwinski, 1996;Martin et al, 1996). Work by Murakami and coworkers (2003) exemplifies this idea well in showing that fibroblasts from the skin of longliving Snell dwarf mice are resistant to multiple forms of cellular stress including heat, paraquat, H2O2, UV light, and the toxic metal cadmium.…”

The role of infant nutrition in the global epidemic of non-communicable disease

“…This hypothesis is strongly supported by data from animals models showing that faster growth in early life is associated with reduced life span (23)(24)(25)(26) , shorter telomere length (a marker of cellular ageing) (23,44) and increased expression of mediators of cellular senescence such as p16 concentrations (44) . However, whether rapid infant growth affects accelerated cellular ageing leading to increased whole body ageing in man is unknown.…”

“…Of relevance to CVD, in the 1970s Hahn found rats overfed during suckling developed higher plasma insulin and cholesterol in adulthood; later, Lewis found overfeeding in infant baboons programmed obesity, an effect that emerged only in adolescence, showing that programmed effects may be 'remembered' but not expressed as a phenotypic consequence until later (3) . Now, extensive evidence in animal models shows that nutrition in early postnatal life programmes the major risk factors for CVD (insulin resistance, obesity, dyslipidaemia and blood pressure (3)(4)(5) ), atherosclerosis (6) and even longevity (23)(24)(25)(26) .…”