The Lifespan Extension Effects of Resveratrol are Conserved in the Honey Bee and May Be Driven by a Mechanism Related to Caloric Restriction

Our interest in healthy aging and in evolutionarily conserved mechanisms of lifespan extension prompted us to investigate whether features of age-related decline in the honey bee could be attenuated with resveratrol. Resveratrol is regarded as a caloric restriction mimetic known to extend lifespan in some but not all model species. The current, prevailing view is that resveratrol works largely by activating signaling pathways. It has also been suggested that resveratrol may act as an antioxidant and confer protection against nervous system impairment and oxidative stress. To test whether honey bee lifespan, learning performance, and food perception could be altered by resveratrol, we supplemented the diets of honey bees and measured lifespan, olfactory learning, and gustatory responsiveness to sucrose. Furthermore, to test the effects of resveratrol under metabolic challenge, we used hyperoxic environments to generate oxidative stress. Under normal oxygen conditions, two resveratrol treatments—30 and 130 μM—lengthened average lifespan in wild-type honey bees by 38% and 33%, respectively. Both resveratrol treatments also lengthened maximum and median lifespan. In contrast, hyperoxic stress abolished the resveratrol life-extension response. Furthermore, resveratrol did not affect learning performance, but did alter gustation. Honey bees that were not fed resveratrol exhibited greater responsiveness to sugar, while those supplemented with resveratrol were less responsive to sugar. We also discovered that individuals fed a high dose of resveratrol—compared to controls—ingested fewer quantities of food under ad libitum feeding conditions

Honeybee Associative Learning Performance and Metabolic Stress Resilience Are Positively Associated

Background: Social-environmental influences can affect animal cognition and health. Also, human socio-economic status is a covariate factor connecting psychometric test-performance (a measure of cognitive ability), educational achievement, lifetime health, and survival. The complimentary hypothesis, that mechanisms in physiology can explain some covariance between the same traits, is disputed. Possible mechanisms involve metabolic biology affecting integrity and stability of physiological systems during development and ageing. Knowledge of these relationships is incomplete, and underlying processes are challenging to reveal in people. Model animals, however, can provide insights into connections between metabolic biology and physiological stability that may aid efforts to reduce human health and longevity disparities. Results: We document a positive correlation between a measure of associative learning performance and the metabolic stress resilience of honeybees. This relationship is independent of social factors, and may provide basic insights into how central nervous system (CNS) function and metabolic biology can be associated. Controlling for social environment, age, and learning motivation in each bee, we establish that learning in Pavlovian conditioning to an odour is positively correlated with individual survival time in hyperoxia. Hyperoxia induces oxidative metabolic damage, and provides a measure of metabolic stress resistance that is often related to overall lifespan in laboratory animals. The positive relationship between Pavlovian learning ability and stress resilience in the bee is not equally established in other model organisms so far

Chloroplasts: The Future of Large-Scale Protein Production

Chloroplast engineering has matured considerably in recent years. It is emerging as a promising tool to address the challenges related to food security, drug production, and sustainable energy posed by an ever-growing world population. Chloroplasts have proven their potential by efficiently expressing transgenes, encapsulating recombinant proteins, and protecting them from cellular machinery, making it possible to obtain highly functional proteins. This quality has also been exploited by interfering RNA technology. In addition to the practical attributes offered by chloroplast transformation, such as the elimination of position effects, polycistronic expression, and massive protein production, the technique represents an advance in biosafety terms; however, even if its great biotechnological potential, crops that have efficiently transformed are still a proof of concept. Despite efforts, other essential crops have remained recalcitrant to chloroplast transformation, which has limited their expansion. In this chapter, we address the most recent advances in this area and the challenges that must be solved to extend the transformation to other crops and become the de facto tool in plant biotechnology

En undersøkelse av stresstoleranse og forlengelse av livsløpet hos bier, Apis mellifera

Many societies and health systems will soon face the unprecedented challenge of burgeoning aged populations. This demographic change will place pressure on social and medical systems, and give rise to questions concerning quality of life. Aging is often characterized by a decreased capacity for stress resistance and cognitive tasks. Thus, a longer life does not necessarily guarantee a prolonged health span, i.e., the time spent as a healthy individual. Additional research is needed to better understand and ultimately influence the connections between longevity, the decline of brain function, and health span. Using the honeybee as a model system, this dissertation examines the relationship between stress and lifespan, the effects of oxidative stress on learning and sensory capacity, and the potential reversal of brain decline. By combining manipulative tools, including the alteration of oxygen environment, RNAi-mediated gene knockdown, and pharmacological intervention with behavioral assays, this dissertation demonstrates that key indicators of health and lifespan can be selectively modulated. Specifically, hyperoxia negatively impacts survivorship and learning performance without compromising gustatory responsiveness. This indicates that peripheral and central brain functions are differentially affected by oxidative stress in honey bees. In addition, these differences in survivorship can be partially explained by vitellogenin, a yolk precursor protein with antioxidant properties that influences social behavior in honey bees. Lastly, the pharmacological compound, resveratrol, extends honey bee lifespan and alters gustatory responsiveness and food consumption. Honey bees fed resveratrol eat less, suggesting that resveratrol-dependent life span extension may be driven by a mechanism related to caloric restriction. The overall aim of these results is to inform research on future therapies focused on slowing or stalling age-related brain decline. Moreover, they illustrate that alternative model systems in aging research can also be informative.Mange samfunn og helsevesen vil I løpet av få år møte en helt ny utfordring med en økende andel eldre befolkning. Denne demografiske endringen vil legge press på sosiale og medisinske systemer og fremme spørsmål i forhold til livskvalitet. Aldring blir ofte karakterisert ved en redusert evne til å mestre stress og kognitive oppgaver. Et lenger livsløp korrelerer derfor ikke nødvendigvis med hvor stor del av livet man er frisk. Ytterligere forskning er nødvendig for å få en bedre forståelse og dermed mulighet til å påvirke sammenhengen mellom livsløp, reduksjon i hjernefunksjon og helse. I denne avhandlingen brukes honningbien som modelldyr for å undersøke forholdet mellom stress og livsløp, effekten av oksidativt stress på læring og sanser, og potensialet for reversering av hjernens aldringsforfall. Ved å kombinere manipulasjonsteknikker som inkluderer endring av oksygennivå, RNAi-mediert gene-knockdown og farmakologiske tiltak i adferdstester viser denne avhandlingen at nøkkelindikatorer for helse og livsløp kan bli selektivt modulert. Spesielt hyperoxi innvirker negativt på overlevelse og læringsevne uten å kompromitere gustatorisk reaksjonsevne. Dette gir indikasjoner om at perifere og sentrale hjernefunksjoner er ulikt berørt av oksidativt stress hos honningbier. Disse forskjellene kan også forklares ved vitellogenin, et precursor protein med antioksidante egenskaper som påvirker sosial adferd hos honningbier. Til slutt; den farmakologiske faktoren, resveratrol forlenger honningbiens livsløp og endrer gustatorisk respons og fôrforbruk. Honningbier som får resveratrol spiser mindre noe som antyder at resveratrol-avhengig økt livsløp kan være styrt av en mekanisme knyttet til kalorirestriksjon. Det overordnede målet med disse resultatene er å opplyse forskning på fremtidig terapi som fokuserer på å bremse eller stagnere aldersrelatert redusert hjernefunksjon. I tillegg illustrerer disse resultatene at alternative modellsystemer i aldringsforskning også kan være informativ

An examination of stress resistance and lifespan extension in the honey bee, Apis mellifera

Many societies and health systems will soon face the unprecedented challenge of burgeoning aged populations. This demographic change will place pressure on social and medical systems, and give rise to questions concerning quality of life. Aging is often characterized by a decreased capacity for stress resistance and cognitive tasks. Thus, a longer life does not necessarily guarantee a prolonged health span, i.e., the time spent as a healthy individual. Additional research is needed to better understand and ultimately influence the connections between longevity, the decline of brain function, and health span. Using the honeybee as a model system, this dissertation examines the relationship between stress and lifespan, the effects of oxidative stress on learning and sensory capacity, and the potential reversal of brain decline. By combining manipulative tools, including the alteration of oxygen environment, RNAi-mediated gene knockdown, and pharmacological intervention with behavioral assays, this dissertation demonstrates that key indicators of health and lifespan can be selectively modulated. Specifically, hyperoxia negatively impacts survivorship and learning performance without compromising gustatory responsiveness. This indicates that peripheral and central brain functions are differentially affected by oxidative stress in honey bees. In addition, these differences in survivorship can be partially explained by vitellogenin, a yolk precursor protein with antioxidant properties that influences social behavior in honey bees. Lastly, the pharmacological compound, resveratrol, extends honey bee lifespan and alters gustatory responsiveness and food consumption. Honey bees fed resveratrol eat less, suggesting that resveratrol-dependent life span extension may be driven by a mechanism related to caloric restriction. The overall aim of these results is to inform research on future therapies focused on slowing or stalling age-related brain decline. Moreover, they illustrate that alternative model systems in aging research can also be informative

Characterization and risk estimate of cancer in patients with primary Sjögren syndrome

Abstract Background The purpose of this study is to characterize the risk of cancer in a large cohort of patients with primary Sjögren syndrome (SjS). Methods We had analyzed the development of cancer in 1300 consecutive patients fulfilling the 2002 SjS classification criteria. The baseline clinical and immunological characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis as predictors of cancer using Cox proportional hazards regression analysis adjusted for age at diagnosis and gender. The sex-and age-specific standardized incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data. Results After a mean follow-up of 91 months, 127 (9.8%) patients developed 133 cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS correlated with the risk of hematological neoplasia and cryoglobulins with a high risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3 levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer, 4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer. Conclusions One third of cancers developed by patients with primary SjS are B-cell lymphomas. The prognostic factors identified at SjS diagnosis differed according to the subtype of B-cell lymphoma developed. Primary SjS is also associated with the development of some non-hematological cancers (thyroid, oral cavity, and stomach)

Additional file 2: Figure S1. of Characterization and risk estimate of cancer in patients with primary Sjögren syndrome

Frequency of the main WHO subtypes of hematological cancer and the corresponding predictive factors identified at SjS diagnosis. (TIF 182 kb