Abstract
Recent experimental studies highlighted the role of hydrogen sulfide (H2S) in aging and longevity. The cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) are the key enzymes responsible for H2S production. Here we investigated the geroprotective effects of CSE and CBS overexpression in Drosophila. Overexpression of CSE did not affect a lifespan and decrease (mitochondrial form of CSE) or increase (cytoplasmic form of CSE) age dynamics of locomotor activity, while overexpression of CBS increase median (by 12.5%) and maximum (by 6.9%) lifespan and locomotor activity. Increasing of both CSE and CBS expression levels resulted in thermotolerance, but the resistance to combination of arid and food-free conditions decreased. The resistance to oxidative stress (paraquat) was not affected in flies with overexpression of CBS and cytoplasmic CSE, but decreased in flies overexpressing mitochondrial form of CSE. Thus, transgene overexpression of the CSE and CBS in Drosophila induce similar effects on stress-resistance and locomotor activity, however lifespan extending effect was revealed for CBS overexpression only.
Highlights
Aging is a multifactorial process characterized by a widespread loss of homeostasis, leading to gradual decrease in functional capacity at all levels of biological organization which, reduced resistance to environmental stresses and exponential increase in probability of death [1]
Using FlyBase search [17] we identified 3 genes responsible for H2S production in Drosophila, CG12264 coding for mitochondria-located enzyme with cystathionine γ‐lyase (CSE) activity [18], CG5345 that codes the cytoplasmlocated orthologue of CSE [11] and CG1753 that is the single homolog of CBS [4]
To further study the role of genes affecting H2S production in longevity of Drosophila, we tested whether ubiquitous over-expression of CBS and CSE under the control of da-GAL4 driver increase resistance to stress factors, prolong lifespan and improve locomotor performance
Summary
Aging is a multifactorial process characterized by a widespread loss of homeostasis, leading to gradual decrease in functional capacity at all levels of biological organization which, reduced resistance to environmental stresses and exponential increase in probability of death [1]. Conserved stress- and nutrientresponsive signaling pathways (such as growth hormone/IGF-1, NAD+/sirtuins, PI3K/AKT/mTOR, AMPK/mTOR and JNK) regulate homeostasis and longevity by coordinating metabolic functions, cell growth and proliferation, and stress responses throughout the organism [1, 2]. The TSP is activated in response to such anti-aging intervention as dietary restriction (DR), and H2S apparently mediates the pleiotropic DR benefits including longevity and stress resistance in different models, from yeast, worms and flies to mice [4, 5]. H2S influences aging-related processes such as cellular bioenergetics, autophagy, inflammation, oxidative stress, proliferation and differentiation of stem cell, cellular senescence, cell death and cellular metabolism [6,7,8,9,10]
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