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.

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 approximately 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.

We developed a complex dietary supplement designed to offset five key mechanisms of aging and tested its effectiveness in ameliorating age-related cognitive decline using a visually cued Morris water maze test. All younger mice (<1 year old) learned the task well. However, older untreated mice (>1 year) were unable to learn the maze even after 5 days, indicative of strong cognitive decline at older ages. In contrast, no cognitive decline was evident in older supplemented mice, even when ∼2 years old. Supplemented older mice were nearly 50% better at locating the platform than age-matched controls. Brain weights of supplemented mice were significantly greater than controls, even at younger ages. Reversal of cognitive decline in activity of complexes III and IV by supplementation was significantly associated with cognitive improvement, implicating energy supply as one possible mechanism. These results represent proof of principle that complex dietary supplements can provide powerful benefits for cognitive function and brain aging.

Studying aging is constrained using vertebrates by their longevity, size, ethical restrictions, and expense. The key insect model, Drosophila melanogaster, is holometabolous. Larvae feed on yeast in moist media and adults sponge food. Most aging studies are restricted to adults. Another key model, the nematode Caenorhabditis elegans, feeds on bacteria in moist media. For either invertebrate refreshing test materials, preventing degradation and obtaining accurate dosing are difficult even with synthetic media. The cricket Acheta domesticus has a short lifespan (∼120 days at 30°C) and is omnivorous. Age-matched cohorts are easily obtained from eggs. The life cycle is hemimetabolous and nymphs eat the same foods as adults. Growth is easily monitored, gender can be differentiated before maturity, and maturation is indicated by wings and mature genitalia. Crickets can be reared in large numbers at low cost. Test materials can be mixed into food and ingestion rates or mass budgets easily assessed. Here, we validate the cricket as a model of aging by testing two fundamental methods of restricting food intake: time-restricted access to food and dietary dilution. Growth, maturation, survivorship, and longevity varied with treatments and genders. Intermittent feeding (which is ineffective in flies) significantly extended longevity of crickets. Dietary dilution also extended longevity via remarkable prolongation of the juvenile period.

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