Simultaneous activation of the hydrogen sulfide biosynthesis genes (CBS and CSE) induces sex-specific geroprotective effects in Drosophila melanogaster.

Hydrogen sulfide (H2S) is one of the most important gasotransmitters that affect lifespan and provide resistance to adverse environmental conditions. Here we investigated geroprotective effects of the individual and simultaneous overexpression of genes encoding key enzymes of H2S biosynthesis - cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE) on D. melanogaster model. Simultaneous overexpression of CBS and CSE resulted in additive (in males) and synergistic (in females) beneficial effects on median lifespan. Individual overexpression of CBS was associated with increased thermotolerance and decreased transcription level of genes encoding stress-responsive transcription factors HIF1 and Hsf, while individual overexpression of CSE was associated with increased resistance to paraquat. Simultaneous overexpression of both genes increased resistance to hyperthermia in old females or paraquat in old males. The obtained results suggest sex-specific epistatic interaction of CBS and CSE overexpression effects on longevity and stress resistance.

Geroprotective potential of genetic and pharmacological interventions to endogenous hydrogen sulfide synthesis in Drosophila melanogaster.

Endogenous hydrogen sulfide (H2S) is a gasotransmitter with a wide range of physiological functions. Aging is accompanied by disruption of H2S homeostasis, therefore, interventions to the processes of H2S metabolism to maintain its balance may have geroprotective potential. Here we demonstrated the additive geroprotective effect of combined genetic and pharmacological interventions to the hydrogen sulfide biosynthesis system by overexpression of cystathionine-ß-synthase and cystathionine-γ-lyase genes and treatment with precursors of H2S synthesis cysteine (Cys) and N-acetyl-L-cysteine (NAC). The obtained results suggest that additive effects of genetic and pharmacological interventions to H2S metabolism may be associated with the complex interaction between beneficial action of H2S production and prevention of adverse effects of excess H2S production by Cys and NAC treatment.

Creatine, Creatine Kinase, and Aging.

With an ever aging population, identifying interventions that can alleviate age-related functional declines has become increasingly important. Dietary supplements have taken center stage based on various health claims and have become a multi-million dollar business. One such supplement is creatine, a major contributor to normal cellular physiology. Creatine, an energy source that can be endogenously synthesized or obtained through diet and supplement, is involved primarily in cellular metabolism via ATP replenishment. The goal of this chapter is to summarize how creatine and its associated enzyme, creatine kinase, act under normal physiological conditions, and how altered levels of either may lead to detrimental functional outcomes. Furthermore, we will focus on the effect of aging on the creatine system and how supplementation may affect the aging process and perhaps reverse it.

Gut microbiota: an ideal biomarker and intervention strategy for aging.

Population aging is a substantial challenge for the global sanitation framework. Unhealthy aging tends to be accompanied by chronic diseases such as cardiovascular disease, diabetes, and cancer, which undermine the welfare of the elderly. Based on the fact that aging is inevitable but retarding aging is attainable, flexible aging characterization and efficient anti-aging become imperative for healthy aging. The gut microbiome, as the most dynamic component interacting with the organism, can affect the aging process through its own structure and metabolites, thus holding the potential to become both an ideal aging-related biomarker and an intervention strategy. This review summarizes the value of applying gut microbiota as aging-related microbial biomarkers in diagnosing aging state and monitoring the effect of anti-aging interventions, ultimately pointing to the future prospects of microbial intervention strategies in maintaining healthy aging.

Saponin-rich extracts from Holothuria leucospilota mediate lifespan extension and stress resistance in Caenorhabditis elegans via daf-16.

Saponins are secondary metabolite compounds that can be found in sea cucumbers (Holothuroidea spp.). However, little is known about how saponin-rich extracts from Holothuria leucospilota can delay and prolong the lifespan of the whole organism. In this study, anti-aging effects of H. leucospilota extracts were studied on Caenorhabditis elegans. NMR analysis revealed that body wall n-butanol-extract of H. leucospilota (BW-BU) is saponin-rich. BW-BU extracts exhibited antioxidant activities by 2,2'-diphenyl-2-picrylhydrazyl assay (EC50  = 10.23 ± 0.12 mg/ml) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid assay (EC50  = 3.91 ± 0.04 mg/ml). BW-BU extracts increased lifespan of L4 and L1 C. elegans (5.92% and 15.76%, respectively), which also increased worm growth, stress resistance, and reduced biomarkers for aging. BW-BU extracts activated DAF-16 nuclear localization and upregulated daf-16 and DAF-16 target genes expression. Taken together, this study revealed the evidences on anti-aging activities of saponin-rich extracts from H. leucospilota, which can extend lifespan of C. elegans via daf-16. PRACTICAL APPLICATIONS: In recent years, age-associated chronic diseases have had a significant impact on quality of life. Many natural compounds exhibit anti-aging activities, especially in sea cucumber, H. leucospilota. Our results indicated that H. leucospilota is good for health. Extracts from H. leucospilota contain a bioactive compound that can be potentially used to promote longevity and disease prevention in aging.