The house cricket is an unrecognized but potentially powerful model for aging intervention studies | Liao | Aging Pathobiology and Therapeutics

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The house cricket is an unrecognized but potentially powerful model for aging intervention studies


Gerald Yu Liaoa, Manuela Rosenfelda, Jackson Wezemana, Warren Ladigesa,*

a Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.

* Corresponding author: Warren Ladiges
Mailing address: Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Email: wladiges@uw.edu

Received: 13 March 2024 / Accepted: 14 March 2024 / Published: 28 March 2024

DOI: 10.31491/APT.2024.03.135

Abstract

Human-based research on the biology of aging poses challenges due to ethical, social, and cost considerations. Animal models offer a pragmatic alternative, although no single model fully replicates all aspects of human aging. One unexplored model for studying aging is the house cricket (Acheta domesticus). House crickets present advantages for aging intervention research, such as consuming an omnivorous diet, availability on a heterogeneous genetic background, short lifespan, and simple but well-defined organ systems. In a preliminary experiment, the effects of flax oil, which is rich in omega-3 fatty acids, on the lifespan of house crickets were investigated. Cold-pressed flax oil was added as a 10% mixture to moist guinea pig chow mash and fed to crickets starting at 8 weeks of age and continuing for 11 weeks until the last cricket died. Results demonstrated a significant extension in survival of crickets fed the flax oil diet, further emphasizing the low cost, simplicity, and short time required to conduct dietary intervention studies in house crickets. Using this observation as a prototype, the house cricket is a promising and deserving model for interventional drug testing based on an aging platform.

Keywords

Aging, house cricket, lifespan, aging intervention, flax oil


Aging is a complex process characterized by functional decline and increasing morbidity, and stands as a predominant risk factor for numerous diseases. Therefore, a better understanding of the underlying mechanisms associated with aging may facilitate the development of new treatments [1]. The complexities of human-based research, including ethical, social, and cost considerations, coupled with a long lifespan, pose significant challenges. Consequently, exploring aging through animal models emerges as a pragmatic alternative. While no single animal model can fully replicate all aspects of aging in humans, a comprehensive understanding of the characteristics of the specific model and a judicious interpretation of the results within its defined limitations can facilitate focused investigations into critical facets of age-related diseases and their associated treatments [2].
Criteria for the selection of effective animal models largely revolve around the translational value to humans in terms of physiological and/or pathological aspects [3]. Rodents, non-human primates, flies (Drosophila melanogaster), and worms (Caenorhabditis elegans) have been extensively used in aging research [4]. Recognition of the challenges associated with vertebrate models, including long lifespan, size, ethical constraints, and cost [5, 6], underscores the importance of integrating translational invertebrate models, particularly in lifespan studies. A significant amount of new knowledge about aging and agerelated diseases has been generated with these models.
Mammalian models of aging have some of the same constraints as humans, while flies and worms have technical constraints. Flies are holometabolous (i.e., have multiple developmental life stages) and most studies are restricted to the adult stage only [5], while worms feed on bacteria and lack a vascular system along with organs that target it (i.e., brain, heart, kidney) [7]. As a result, test materials and accurate dosing are technically demanding. Acheta domesticus, or more commonly known as the "house cricket", is a promising model for the study of aging and age-related diseases for several reasons. 1) They are omnivorous with rudimentary but well-defined organ systems (Figure 1); 2) They are relatively easy to rear at 30-32 ℃ in large quantities, small areas, and at low cost [8-10]; 3) Crickets are hemimetabolous with an average lifespan of 4 months, with juveniles sharing the same diet as adults; 4) Crickets have a visually distinguishable sexual maturity between developmental stages and adults [9-11]; 5) Neurogenesis occurs in the cricket brain in an area analogous to the mammalian hippocampus [12-14]; 6) Cognitive and non-cognitive behavioral tests are easily performed in crickets [15].


Figure 1. Internal structures of the domestic house cricket.

These characteristics make house crickets ideal for aging studies. For example, our laboratory has observed an increase in lifespan when crickets were fed flax oil added to their diet. Genetically heterogeneous house crickets were obtained from Fluker Farms (Louisiana) at 8 weeks of age and fed guinea pig chow or guinea chow supplemented with 10% cold-pressed flax oil (Barlean's). They were housed in a transparent and aerated plastic box (36 × 36 × 20 cm) containing an egg carton shelter, a tray with a moistened sponge, and a food tray at an environmental temperature of 20-21℃ and a 12 h on/12 h off light cycle. The guinea pig chow contained protein 16%, fat 3.5%, fiber 12.5%, ash 6%, calcium 0.8%, phosphorus 0.6%, copper sulfate 15 mg/kg, vitamin A 6000 IU/kg, vitamin C 300 mg/kg, vitamin D3 520 IU/kg, vitamin E 24 IU/kg and was prepared as a mash with 30 g of chow and 300 mL of sterilized distilled water to provide a consistency readily ingested by the crickets.
Crickets fed guinea chow with flax oil had a significant increase in lifespan compared to crickets fed just guinea pig chow (Figure 2). The 50 percent survival rate was 82 and 94 days, respectively and the 10 percent survival rate was 109 and 136 days, respectively. Flax oil is rich in polyunsaturated omega-3 fatty acids (PUFA), particularly alpha-linolenic acid, which has been shown to exhibit anti-inflammatory and antioxidant effects [16]. Crickets have a simplified gut structure consisting of a single layer of epithelium with various cells such as enterocytes responsible for nutrient absorption [17], including dietary lipids such as PUFAs [18]. While the effects of PUFAs are not well-documented in the insect digestive system, they are known to improve the integrity of the intestinal epithelial barrier in mammals by preventing changes in epithelial permeability, inhibiting the production of proinflammatory molecules, and enhancing the production of anti-inflammatory molecules [19-21].
The optimal advantages of crickets as an animal model of aging, along with our preliminary observations, provide a strong rationale for conducting more in-depth studies using house crickets to test a variety of intervention strategies using both lifespan and cross-sectional approaches.

Figure 2. Beginning at 8 weeks of age, house crickets were fed guinea pig chow with 10% flax oil versus crickets fed just guinea pig chow. Lifespan in the two cohorts was assessed using Kaplan-Meier (logrank) survival analysis. Time points were assigned equal weight using a Mantel-Cox test. P < 0.05. N = 29-30 per cohort.

Declarations

Financial support and sponsorship

Supported by the National Institute on Aging grant R01 AG057381 (Ladiges, PI).

Conflicts of interest

Warren Ladiges is a member of the editorial board of Aging Pathobiology and Therapeutics. The authors declare that they have no conflicts and were not involved in the journal's review or decision regarding this manuscript.

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