C. David Rollo

Growth negatively impacts the life span of mammals.

SUMMARY 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.

Dietary amelioration of locomotor, neurotransmitter and mitochondrial aging

Aging degrades motivation, cognition, sensory modalities and physical capacities, essentially dimming zestful living. Bradykinesis (declining physical movement) is a highly reliable biomarker of aging and mortality risk. Mice fed a complex dietary supplement (DSP) designed to ameliorate five mechanisms associated with aging showed no loss of total daily locomotion compared with >50% decrement in old untreated mice. This was associated with boosted striatal neuropeptide Y, reversal of age-related declines in mitochondrial complex III activity in brain and amelioration of oxidative stress (brain protein carbonyls). Supplemented mice expressed ∼50% fewer mitochondrial protein carbonyls per unit of complex III activity. Reduction of free radical production by mitochondria may explain the exceptional longevity of birds and dietary restricted animals and no DSP is known to impact this mechanism. Functional benefits greatly exceeded the modest longevity increases documented for supplemented normal mice. Regardless, for aging humans maintaining zestful health and performance into later years may provide greater social and economic benefits than simply prolonging lifespan. Although identifying the role of specific ingredients and interactions remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.

Radiation-induced apoptosis in mouse lymphocytes is modified by a complex dietary supplement: the effect of genotype and gender

This study examined whether radiation sensitivity measured by lymphocyte apoptosis could be ameliorated by a complex anti-oxidant/anti-ageing dietary supplement. We also examined lymphocytes from both genders of normal (Nr) mice as well as transgenic growth hormone (Tg) mice that express strongly elevated reactive oxygen species processes and a progeroid syndrome of accelerated ageing. We introduce Tg mice as a potentially valuable new model to study radiation sensitivity. Isolated lymphocytes from all experimental groups were exposed to gamma radiation and the time course of apoptosis was measured in vitro. Kinetics of radiation-induced apoptosis was similar among groups, which peaked at 8 h, but maximal levels differed significantly between groups. Nr male mice had 60% lower levels of radiation-induced apoptosis than Tg males, supporting our hypothesis that Tg mice would be radiation sensitive. The dietary supplement protected lymphocytes in male mice of both strains, with proportionally greater reductions in Tg mice. Lymphocytes from female mice (both Nr and Tg) were highly radiation resistant compared to males and the supplement provided no additional benefit at the doses used in this study. These results highlight that radiation-induced apoptosis is complex and is modified by genotype, dietary supplements and gender.

Dopamine and Aging: Intersecting Facets

Aging encompasses life itself so understanding requires frameworks that forge unity amidst complexity. The free radical theory of aging is one example. The original focus on damage was augmented recently by appreciation that reactive oxygen and nitrogen species are essential to normal signaling and cell function. This paradigm is currently undergoing an explosive expansion fueled by the discovery that regulatory organization is a merry-go-round of redox cycling seamlessly fused to endogenous clocks. This might best be described as an “Electroplasmic Cycle.” This is certainly applicable to dopaminergic neurons with their exceptional metabolic, electrical and rhythmic properties. Here I review normal aging of dopamine systems to highlight them as a valuable model. I then examine the possible integration of free radical and ion channel theories of aging. Finally, I incorporate clocks and explore the multifaceted implications of electroplasmic cycles with special emphasis on dopamine.

Consequences of competition on the reproduction and mortality of three species of terrestrial slugs

The interaction of three species of terrestrial slugs was studied in six field cages containing monocultures and 2-way combinations.A. columbianus andA. ater were non-aggressive species andL. maximus was highly aggressive during the summer. All three species were similar in body design and resource utilization. Reproduction (egg size, eggs/batch, number of batches, wet-weight productivity) and mortality were monitored through the 1977 season.L. maximus drastically reduced reproductive success of the non-aggressive slugs and increased their mortality. There were also significant interactions between the non-aggressive species. Compared to other invertebrates, the life history characteristics ofA. columbianus are stronglyK-selected and probably evolved through intraspecific exploitative competition in predictable, stable forest habitats.A. ater is best classified as a refugingr-selected species adapted to less predictable, unstable field environments.L. maximus appears to be α-selected and its overall design is suited to density-dependent regulation in fields.

Resource allocation and time budgeting in adults of the cockroach,Periplaneta americana: The interaction of behaviour and metabolic reserves

Activity (to food, water and shelter) and resource allocation (mass budget, and size of various body components) were examined in populations of adultPeriplaneta americana subjected to periods of starvation or sugar feeding. Following 13 days of starvation, roaches ate 5 times their normal daily ration and feeding required about 20 days to return to pre-starvation levels. When sucrose was substituted for the usual dog-food diet for 13 days, there was also a large increase in feeding initially. When the dog food was re-established, however, there was very little feeding for about one week. Although reproduction was markedly curtailed by starvation, females fed sucrose continued reproducing for at least 59 days. The results suggested that the roaches were mainly energy limited. Although the consumption of roaches was strongly affected by reserve depletion, eating was a small component of the time budget, and overall activity was relatively unchanged by starvation or sugar-feeding. There was a slight decrease in activity during starvation, but the circadian pattern remained unchanged. Females carrying oöthecae were highly active and were apparently attracted to food (even though they ate little). Thus the activity of the population was dominated by circadian rhythmicity and the reproductive cycle.

Consequences of competition on the time budgets, growth and distributions of three species of terrestrial slugs

The behavioural time budgets of two non-aggressive slugs and one aggreessive species were evaluated in monocultures or in 2-way combinations in field cages. The seasonal time budgets ofL. maximus, A. ater andA. columbianus in monoculture were remarkably similar despite their strong differences in physiological resource allocation. Similarity in physical design and resource utilization appeared to be more important determinants of behaviour. The time budgets showed distinct seasonal patterns associated with underlying physiological demands for reserve accumulation, sperm acquisition and oviposition.A. ater andL. maximus displayed a definite dispersal phase associated with femalephase maturation. In combination,A. ater andA. columbianus had no detectable effect on one another’s time budgets.L. maximus disrupted nearly every category of behaviour in these non-aggressive species, but its own time budget was not significantly different in the monoculture or in the two combinations, except for minor effects on resting and sexual behaviour.L. maximus appeared to be adapted to maximize behavioural disturbance of interspecific competitors while minimizing intraspecific effects.

A complex dietary supplement modulates nitrative stress in normal mice and in a new mouse model of nitrative stress and cognitive aging.

We examined whether transgenic growth hormone mice (Tg) that exhibit accelerated cognitive aging and exceptional free radical damage also express elevated nitrative stress. We characterized age-related patterns of 3-nitrotyrosine (3-NT) in brain homogenate and mitochondria of Tg and normal (Nr) mice as modulated by a complex anti-aging dietary supplement. Levels of 3-NT rose rapidly with age in Tg brain homogenate whereas normal controls maintained constant lower levels. The age-related slope for 3-NT was 3.6-fold steeper in untreated Tg compared to treated Tg (p<0.009), although treated Tg showed elevation in youth. Opposite to Tg, treated Nr mice had reduced 3-NT in youth (p<0.02). The age-related pattern of mitochondrial 3-NT in Nr mice was parabolic (p<0.005). Remarkably, levels in treated Nr were reduced by ~50% (p<0.0007). Untreated Tg showed strongly increasing mitochondrial 3-NT with higher mitochondrial activity (p<0.01) whereas treated Tg showed lower nitrosylation at higher levels of mitochondrial activity. Tg mice also expressed a postural abnormality that is a biomarker of neurodegeneration and/or nitrative stress. Tg represent a promising new model of nitrative stress associated with brain deterioration and results provide proof of principle that complex dietary supplements may be ameliorating.

Trojan Genes and Transparent Genomes: Sexual Selection, Regulatory Evolution and the Real Hopeful Monsters

Potential impacts of genetically modified (GM) animals in natural environments are explored in a framework of regulatory evolution. Transgenic growth hormone animals express remarkable alterations and plasticity in development, physiology and behavior in response to environmental factors (nutrition, temperature, photoperiod), suggesting that standard laboratory assessments are likely to underestimate their evolutionary potential. Sexual selection is examined in the context of female self-referent appraisal of male fitness that reflects performance in the species-specific niche. Wild-type females may recognize and discriminate against GM males (the Transparent Genome Hypothesis) but if accepted as mates, pleiotropic disruption associated with GMs may reduce fitness of the natural population (the Trojan Gene Hypothesis). Alternatively, facilitation of regulatory evolution by sexual reproduction (recombination and segregation) may derive modifier selection, masking, integration, or niche shifts. Other aspects explored include mutation theory, purging, pleiotropy, epigenetics and plasticity, behavior and the Bruce effect, and mismatch of genetic or epigenetic background between GM stock and natural populations.

A multi-ingredient athletic supplement disproportionately enhances hind leg musculature, jumping performance, and spontaneous locomotion in crickets (Acheta domesticus)

Nutrition is a key component of life‐history theory with profound impacts on fitness traits. We examined lifetime impacts of a multi‐ingredient athletic supplement (MAS) on physical performance, anatomical morphology, survivorship, and general life‐history features in the house cricket, Acheta domesticus (L.) (Orthoptera: Gryllidae). The MAS was formulated using 13 nutraceutical supplements that are commonly used by human athletes specifically to improve athletic performance. Cricket doses were based on human doses adjusted for body size and metabolic rate. Markers of athletic performance included: jumping distance, spontaneous locomotor activity, and morphology of the hind legs (femurs). Supplemented adult crickets jumped ca. 25% further and expressed elevated spontaneous locomotion relative to controls. The MAS disproportionately increased hind leg femur length and width. Life‐history endpoints included survivorship, juvenile growth rate, maturation age, and mature body size. Supplemented crickets showed faster juvenile growth and earlier maturation, but no change in final adult size. A 20% increase in mean survivorship (extending into older ages) was also documented. Crickets represent an excellent new model for assessing athletic diets and associated performance criteria. Finally, as experimental animals were untrained, we argue that our supplement may represent a novel ‘exercise mimetic’ that impacts both performance and survivorship.