The role of Biophotons in cellular senescence.

Senescence is the irreversible arrest of cell proliferation. While serving as a natural barrier against mutation progression, senescence's metabolic activity and elevated ROS levels can pose significant health risks. Concurrently, cellular metabolic processes, including mitochondrial respiration, are known to emit ultra-weak photons (biophotons), primarily generated through ROS production. There is increasing evidence that cells can influence each other non-chemically via biophotons. In this study, I aim to elucidate the potential impact of both intrinsic biophotonic emissions and extrinsic light exposure on cellular senescence. To achieve this, I developed, utilising doxorubicin (Dox), four different senescence models: two cancer (MCF7 breast and A549 lung) and two non-cancer cell lines (MCF10A breast and IMR-90 lung fibroblasts). Dox-treated cells showed senescentrelated physiological changes, including decreased proliferation (P ≤ 0.05), increased betagalactosidase activity (P ≤ 0.001), increased ROS (P ≤ 0.01), mitochondrial membrane potential (P ≤ 0.01) and calcium (Ca2+) levels (P ≤ 0.01). Then, to investigate potential biophotonic communication, I utilised a customised assay to detect non-chemical signalling, showing an increasing oxygen consumption rate in isolated mitochondria from senescent MCF10A (0.0029% per second; P < 0.0001), MCF7 (0.0042% per second; P < 0.0001) and A549 cells (0.0017% per second; P < 0.0001). Additionally, photons emitted by isolated mitochondria from senescent MCF10A cells were monitored via an ultra-sensitive light detector, confirming biophotonic activity (1.86 ± 0.82 photons per 10 seconds; P ≤ 0.05). Further comparison of mitochondrial non-chemical signalling between senescent and nonsenescent cells revealed distinct biophotonic communication across the three tested senescent cell lines, with significant differences compared to their non-senescent cellular controls (MCF10A and MCF7: P ≤ 0.0001; A549: P ≤ 0.05). In addition, I have shown that cells interact with external light, as exposure to near-infrared (NIR) light (734 nm) increased senescent levels in the cancer cell lines (P ≤ 0.01), associated with increased ROS production (P ≤ 0.05), mitochondrial membrane potential (P ≤ 0.05), and intracellular Ca2+ levels (P ≤ 0.05), but not in the two non-cancer populations. My work demonstrates that biophotons and extracellular light (NIR light exposure) may play a significant role in senescence and open novel insights for non-invasively influencing cellular processes.