Insulin receptor substrate (IRS) gene knockdown accelerates behavioral maturation and shortens lifespan in honeybee workers.

Authors: Ihle, Kate; MUTTI, NAVDEEP - Arizona State University; KAFTANOGLU, OSMAN - Arizona State University; AMDAM, GRO - Arizona State University

Submitted to: Insects
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2021
Publication Date: 2/7/2022
Citation: Ihle, K.E., Mutti, N.S., Kaftanoglu, O., Amdam, G.V. 2019. Insulin receptor substrate (IRS) gene knockdown accelerates behavioral maturation and shortens lifespan in honeybee workers. Insects. 10:1-14. https://doi.org/10.3390/ insects10110390.
DOI: https://doi.org/10.3390/insects10110390

Interpretive Summary: In most animals, reduced calorie intake or suppression of molecular or physiological indicators of nutrition such as insulin signaling increase lifespan. Honey bee workers show the same pattern in the laboratory, but that setting is very different from their highly social colonies. In a honey bee colony, food and nutrition play important roles in regulating the social structure of the colony and in the speed at which worker bees age suggesting that the relationship between nutrition and lifespan might be affected. As young bees, workers have a diet rich in protein and lipids. These young bees called nurses have large nutrient stores and produce “jellies” that are fed to the developing brood and other nestmates. As the bees age, their internal nutrient stores decline and they change tasks from feeding the colony directly, to collecting food from the field as foragers. The speed at which a bee ages from a nurse to a forager plays a large role in determining her lifespan. We asked how the link between lifespan and nutrient sensing is affected by the highly social colony environment by suppressing expression of the Insulin receptor substrate (IRS), a gene in the insulin/insulin like signaling pathway. This pathway is involved in nutrient sensing and experimental reduction has been shown to increase lifespan in many animals. We found that reducing IRS expression led to shorter lifespans in worker honey bees. We believe that this effect is due to the role that nutrition plays in the social organization of a colony and especially its role in the nurse to forager transition. Understanding how social environments affect aging can give us insights on how to keep bees healthy and how important social interactions might be for aging in other species.

Technical Abstract: In animals, dietary restriction or suppression of genes involved in nutrient sensing tends to increase lifespan. In contrast, food restriction in honeybees (Apis mellifera) shortens lifespan by accelerating a behavioural maturation program that culminates in leaving the nest as a forager. Foraging is metabolically demanding and risky, and foragers experience increased rates of aging and mortality. Food-deprived worker bees forage at younger ages and are expected to live shorter lives. We tested whether suppression of a molecular nutrient sensing pathway is sufficient to accelerate the behavioural transition to foraging and shorten worker life. To archive this, we reduced expression of the insulin receptor substrate (IRS) gene via RNA interference in two selected lines of honeybees used to control for behavioural and genetic variation. IRS encodes a membrane-associated protein in the insulin/insulin-like signalling (IIS) pathway that is central to nutrient sensing in animals. We measured foraging onset and lifespan and found that suppression of IRS reduced worker bee lifespan in both genotypes, and that this effect was largely driven by an earlier onset of foraging behaviour in a genotype-conditional manner. Our results provide the first direct evidence that an IIS pathway gene influences behavioural maturation and lifespan in honeybees, and highlight the importance of the social environment when investigating the regulation of aging and lifespan in social animals.