[SCIENCE MONDAY] - Cellular Senescence and Tumor Transformation: A Delicate Balance Between Growth and Oxidative Stress

Cellular senescence is a process in which cells stop dividing but remain metabolically active. It can occur naturally in normal cells as part of aging, or in tumor cells—either spontaneously or as a response to stress that halts their growth. In all these situations, the level of reactive oxygen species (ROS)—molecules associated with oxidative stress—plays a key role, influencing the cell’s internal redox balance.

This study explored the relationship between cellular senescence and cell transformation by comparing three types of cell cultures derived from the NIH/3T3 cell line:

• NIHb, used as a reference;
• NIHs, showing features of tumor transformation;
• NIHv, showing features of senescence.

The cells were examined before and after exposure to hydrogen peroxide (H₂O₂), a molecule known to induce oxidative stress. This experimental model aims to mimic the heterogeneity seen in some tumors, where populations of cells with different degrees of transformation or senescence coexist.

The team analyzed multiple morphological and functional aspects, including the cell cycle, the content and activity of mitochondria and lysosomes, superoxide production, autophagic activity, and the accumulation of lipofuscin, a pigment considered a hallmark of cellular aging.

The results revealed that:

• in reference cells (NIHb), H₂O₂ treatment had minimal effects;
• in senescent cells (NIHv), the senescent state remained stable;
• in transformed cells (NIHs), however, significant changes occurred.

Specifically, the NIHs cells began to show typical features of senescence, such as SA-β-galactosidase positivity, reduced proliferation, and altered mitochondrial and lysosomal function. Moreover, the increase in autophagy and lipofuscin accumulation suggests that even the cytoplasmic activity of these cells had shifted toward a senescent-like state.

The different responses to hydrogen peroxide seemed to depend not only on the cells’ baseline proliferative activity but also on their specific redox state—that is, the balance between ROS generated internally and those produced by the treatment.

In the case of NIHs cells, the slower progression through the cell cycle appeared to be linked to a dynamic interaction between mitochondria and lysosomes. This finding suggests that, in certain transformed cells, changes in the redox state can trigger morphological and functional traits typical of senescence.