Milen I. Georgiev^1,2

1 Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria

2 Laboratory of Metabolomics, Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria

Obesity presents a significant challenge to the modern society, imposing a substantial burden on health systems and individuals alike. Nowadays, more than a billion people globally are considered obese, a condition that does not solely refer to weight management but rather to mitigating its far-reaching consequences on healthspan and lifespan [1]. Individuals diagnosed with obesity are predisposed to comorbidities including type 2 diabetes, cardiovascular disease, and metabolic complications often referred to as metabolic syndrome. Most importantly, obesity is associated with a reduction in disease-free years, an excess risk of premature death, and accelerated aging [1, 2].

On the other hand, we live in a rapidly aging world, with an expectancy of more than a 2 billion people aged 65 years (or older) by 2050, alongside a rising proportion of age-related diseases. Thus, both obesity and ageing are, per se, different sides of the same coin and represent healthcare burden on our society [1, 2]. The development of strategies targeting both of these processes now becomes a challenge for science. Central to this pursuit is the recognition that metabolic health serves as a cornerstone for both healthy weight maintenance and prolonged lifespan [2]. Additionally, key molecular pathways attributed to nutrient signalling that are implicated in obesity progression, intersect with those fundamental to longevity, suggesting potential shared targets for intervention [2].

Utilizing the model organism Caenorhabditis elegans (nematode), along with combining omics and molecular pharmacology approaches, our research focuses on the discovery of natural products that target these shared pathways [1-4]. Through our approach, we aim not only to mitigate the adverse effects of obesity but also to uncover novel strategies for promoting healthy aging and longevity.

Acknowledgements: MIG acknowledges financial support from the European Regional Development Fund through Programme Research Innovation and Digitalisation for Smart Transformation, Grant agreement № BG16RFPR002-1.014-0003-C01.

References:

[1] Savova MS, Mihaylova LV, Tews D, Wabitsch M, Georgiev MI (2023) Targeting PI3K/AKT signaling pathway in obesity. Biomedicine & Pharmacotherapy, 159: 114244.

[2] Todorova MN, Savova MS, Mihaylova LV, Georgiev MI (2024) Nurturing longevity through natural compounds: Where do we stand, and where do we go? Food Frontiers, 5: 267-310. 

[3] Savova MS, Vasileva LV, Mladenova SG, Amirova KM, Ferrante C, Orlando G, Wabitsch M, Georgiev MI (2021) Ziziphus jujuba Mill. leaf extract restrains adipogenesis by targeting PI3K/AKT signaling pathway. Biomedicine & Pharmacotherapy, 141: 111934. 

[4] Todorova MN, Savova MS, Mihaylova LV, Georgiev MI (2024) Punica granatum L. leaf extract enhances stress tolerance and promotes healthy longevity through HLH-30/TFEB, DAF16/FOXO, and SKN1/NRF2 crosstalk in Caenorhabditis elegans. Phytomedicine, 134: 155971.

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