No 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.

Illness, death, and costs of immunity and injury strongly select for avoidance of predators or contagion. Ants, cockroaches, and collembola recognize their dead using unsaturated fatty acids (e.g., oleic or linoleic acid) as ''necromone'' cues. Ants, bees, and termites remove dead from their nests (necrophoric behavior) whereas semisocial species seal off corpses or simply avoid their dead or injured (necrophobic behavior). Alarm and avoidance responses to exudates from injured conspecifics are widespread. This involves diverse pheromones, complex chemistry and learning. We hypothesized that necromones are a phylogenetically ancient class of related signals and predicted that terrestrial Isopoda (that strongly aggregate and lack known dispersants) would avoid body fluids and corpses using fatty acid ''necromones.'' Isopods were repelled by crushed conspecifics (blood), intact corpses, and alcohol extracts of bodies. As predicted, the repellent fraction contained oleic and linoleic acids and authentic standards repelled several isopod species. We further predicted a priori that social caterpillars (lacking known dispersants) would be repelled by their own body fluids and unsaturated fatty acids. Both tent caterpillars and fall webworms avoided branches treated with conspecific body fluid. Oleic and linoleic acids were also strongly avoided by both species. Necromone signaling appears widespread and likely traces to aquatic ancestors pre-dating the divergence of the Crustacea and Hexapoda at least 420 million years ago.

Transgenic growth hormone mice lived half as long as normal on a 23% protein diet. Longevities of both transgenic and control mice on a 38% protein diet were half those on 23% protein food. We hypothesized that transgenic mice are energetically constrained by their rapid growth, so energy supplements might improve "longevity assurance investments." As predicted, sucrose supplements extended the longevity of transgenic females (from a mean of 3 15 to 4 19 d). We measured two key biomarkers of aging (in brain, heart, liver, musculature, and kidneys) to test whether aging of these mice conformed to the free radical theory. Transgenic mice showed elevated levels of both superoxide radical (SOR) and lipid peroxidation (LP) compared with controls. The pattern of SOR and LP levels across kinds of mice and diets supported a free radical interpretation of aging and suggested that energy supply (protein or sugar) may impact longevity. The brain and heart were key biomarkers of longevity. LP levels in either organ explained 89% of the variation in longevity associated with genotype, sex, and diet. If combined with dietary restriction, this system should yield an 8-fold range in longevity, representing a powerful new tool for research into life histories and gerontology.RCsumC : Les souris transgkniques quant 2i l'hormone de croissance vivent la moitiC moins longtemps que normalement lorsqu'elles sont soumises 2i un rCgime contenant 23% de protCines. La longCvitC des souris transgkniques et des souris tCmoins nourries 2i un regime contenant 38% de protCines Cquivaut 2i la moitiC de celle des souris nourries 2i un rCgime contenant 23% de protCines. Nous posons en hypothkse que les souris transgkniques subissent des contraintes CnergCtiques imposCes par leur croissance rapide et que des supplCments CnergCtiques pourraient amCliorer leurs investissements en vue d'une 1ongCvitC accrue. Tel que prCdit, des supplCments de sucrose ont entrain6 une amklioration de la longCvitC chez des femelles transgkniques (de 3 15 jours en moyenne 2i 419 jours). Nous avons mesurC deux importants marqueurs biotiques du vieillissement (dans le cerveau, le coeur, le foie, la musculature et les reins) de f a~o n 2i dCterminer si le vieillissement de ces souris est conforme 2i la thCorie des radicaux libres. Les souris transgkniques ont des concentrations plus ClevCes du radical superoxyde (SOR) et des taux plus ClevCs de peroxydation des lipides (LP) que les souris tCmoins. Les patterns de SOR et de LP chez les diffkrents types de souris soumis 2i divers rCgimes alimentaires appuient la thCorie des radicaux libres pour expliquer le vieillissement et indiquent que les apports CnergCtiques (protCines ou sucres) peuvent avoir un impact sur la 1ongCvitC. Le cerveau et le coeur sont des indicateurs biologiques importants de la 1ongCvitC. L'importance de LP dans les deux organes explique 89% de la variation de la 1ongCvitC reliCe au genotype, au sexe et au rCgime alimentaire. CombinC 2i des restrictions alimentaires, ce systkme peut permettre une Ctendue d...

We previously found that transgenic mice overexpressing growth hormone (TGM) have elevated and progressively increasing free radical processes in brain that strongly correlates with reduced survivorship. Young mature TGM, however, displayed vastly enhanced learning of an eight-choice cued maze and qualitatively different learning curves than normal controls. Here we document the age-related patterns in learning ability of TGM and normal mice. Learning appeared inferior in both genotypes of very young mice but TGM were confirmed to be superior to normal mice upon maturity. Older TGM, however, showed rapid age-related loss of their exceptional learning, whereas normal mice at 1 year of age showed little change. The cognitive decline of TGM was abolished by a complex "anti-aging" dietary supplement formulated to promote membrane and mitochondrial integrity, increase insulin sensitivity, reduce reactive oxygen and nitrogen species, and ameliorate inflammation. Results are discussed in the context of reactive oxygen and nitrogen species, long-term potentiation, learning, aging and neuropathology, based on known impacts of the growth hormone axis on the brain, and characteristics of TGM.