Increased workloads in the 21st century are a primary driver of chronic health conditions. Data from a joint study by the International Labour Organization (ILO) and the World Health Organization (WHO) showed that 488 million workers globally, representing 8.9% of the workforce, exceeded 55 working hours per week in 2016 (Figure 1). This issue is most pronounced in the 35-39 age group, with nearly 20% of them working these long hours (Figure 2). The global number of individuals working excessively rose by 9% from 2000 to 2016, highlighting long working hours as a significant and growing health concern.

Prolonged work hours negatively impact human physiology through several interconnected pathways. Chronic sleep deprivation disrupts circadian rhythms and suppresses key hormones like melatonin, increasing risks for obesity, immune dysfunction, and cardiovascular disease. Sedentary work habits impair circulation and metabolism, contributing to musculoskeletal conditions like back pain, diabetes, and varicose veins. Unhealthy dietary patterns involving high-fat and high-sodium foods place additional stress on the body's metabolism, promoting non-alcoholic fatty liver disease and chronic inflammation. Sustained psychosocial pressure also hyperstimulates the hypothalamic-pituitary-adrenal axis, leading to an overproduction of cortisol which can cause insomnia, dermatitis, and heightened cardiovascular vulnerability. Together, these factors create a self-perpetuating cycle of physiological decline and chronic fatigue that is often resistant to rest.
Epidemiological studies confirm the link between long working hours and increased mortality. A multi-cohort study in The Lancet Regional Health – Europe found that individuals working over 55 hours per week face a 52% higher risk of cardiovascular death before age 65. Globally, long work hours were linked to an estimated 745,000 deaths from ischemic heart disease and stroke in 2016, with fatalities from ischemic heart disease rising 42% and from stroke 19% between 2000 and 2016. Further evidence in Nature Reviews Cardiology explains the biological mechanism: chronic psychological stress activates neuroendocrine pathways that damage blood vessels, driving a destructive cycle of occupational burnout, hypertension, and cardiovascular disease (Figure 3).

Known as the "Ginseng of the Highlands" for its ability to combat hypoxia and fatigue, Salidroside is a key component of traditional Tibetan medicine with diverse pharmacological activities (Figure. 4). Its neuroprotective and cardiovascular functions are particularly notable. In neuronal models, it mitigates oxidative stress via the Nrf2/HO-1 pathway, inhibits neuroinflammation by regulating the NLRP3 inflammasome, and shows potential in ameliorating pathologies of Alzheimer's and Parkinson's diseases. For cardiovascular protection, it protects myocardial tissue from ischemia-reperfusion damage by reducing the expression of adhesion molecules and regulating PI3K/Akt signaling. Its broader therapeutic properties—including anti-inflammatory, anti-fibrotic, and anti-cancer effects—support its application in altitude medicine, chronic inflammatory diseases, and adjunctive cancer therapy. In China, numerous approved salidroside-based drugs and health products are used to treat conditions like cardiovascular disease, radiation-induced lung injury, and acute mountain sickness.


Salidroside is a phenolic glycoside compound principally extracted from plants of the genus Rhodiola, which are extensively distributed in high-altitude regions of Eurasia. China, particularly the Qinghai–Tibetan Plateau, is the global center of Rhodiola biodiversity, with 73 species, 2 subspecies, and 7 varieties—a total of approximately 85% of the world's known taxa. The low growth rate (generally 7–8 years) of the species and the harsh ecological environment have caused the wild populations to be vulnerable. Compounding the issue, the inherent content of salidroside in these plants is not high, at just 0.5% to 0.8%, and this has created a long-standing imbalance between supply and demand.

Traditional chemical synthesis of salidroside involves Koenigs-Knorr type glycosylation reactions. While this approach can achieve efficiencies between 20% and 70%, it is hindered by unstable catalysts, severe reaction conditions, and environmental issues like halogenated byproducts and laborious purification.
In contrast, synthetic biology provides a scalable and sustainable alternative. Through metabolic engineering, microbial hosts like Escherichia coli and Saccharomyces cerevisiae are genetically modified to produce salidroside from glucose (Figure 5). These recombinant strains achieve gram-per-liter production titers, far exceeding the yields from natural plant extraction. The biosynthetic approach enhances process efficiency and alleviates environmental pressure, offering an eco-friendly route for industrial-scale production.

In response to the rising incidence of cardiovascular disease linked to overwork, our iGEM project focuses on the therapeutic compound salidroside. While salidroside is a safe cardioprotective agent, its availability is severely restricted by unsustainable natural sourcing. We are therefore applying synthetic biology principles to engineer a novel biosynthetic pathway for salidroside production. The goal is to create a scalable and reliable supply chain, making this critical compound more accessible for widespread health applications. Curious about our strategy used in this project? Please explore our Design page.

1. Ervasti, Jenni et al. “Long working hours and risk of 50 health conditions and mortality outcomes: a multicohort study in four European countries.” The Lancet regional health. Europe vol. 11 100212. 6 Sep. 2021, doi:10.1016/j.lanepe.2021.100212
2. Pega, F. et al. Global, regional, and national burdens of ischemic heart disease and stroke attributable to exposure to long working hours for 194 countries, 2000–2016. Environment International 2021, 149, 106595.
3. Li, J. et al. The effect of exposure to long working hours on ischemic heart disease: a systematic review and meta‐analysis from the WHO/ILO Joint Estimates. Environment International 2020, 142, 105739.
4. Kivimäki, M. et al. Job strain as a risk factor for coronary heart disease: a collaborative meta‑analysis of individual participant data. The Lancet 2012, 380 (9852), 1491–1497.
5. Han, J. et al. Therapeutic potential and molecular mechanisms of salidroside in treating ischemic diseases. Frontiers in Pharmacology 2022, 13, 974775.
6. Chen, P. et al. Protective effects of salidroside on cardiac function in mice—A study in myocardial infarction model. Scientific Reports 2019, 9, 215.