This proposed review aims to shed light on the major genetic and epigenetic contributions to the ageing process and longevity of individuals. In this context, we summarize the state of knowledge on the most important longevity and ageing genetic variants, and their interactions with the environment, in achieving a healthy lifespan. We also explore the contribution of lifestyle and the influence of non-heritable environmental factors on ageing (i.e., epigenetics). Accordingly, we discuss the role of inflammageing as one of the major targets to overcome morbidity and mortality in older people for the maintenance of healthy ageing. This more integrated view of longevity will display not only the underlying mechanisms at play but also invites the reader to rethink both our ageing process and our attitudes toward age.

Glioblastoma (GBM), a highly malignant brain tumor, arises within a complex microenvironment that plays a critical role in facilitating tumor progression, ensuring survival, and enabling immune evasion, ultimately contributing to therapeutic resistance. Cancer-associated fibrosis is increasingly recognized as a key factor in the tumor pathophysiology, particularly in extracranial cancers, and reported therapeutic strategies in several cancers consist of the current use of the standard-of-care treatment combined with anti-fibrotic drugs. However, it remains unclear how the fibrotic changes associated with the GBM microenvironment contribute to the transformation of GBM from a chemosensitive state to a chemoresistant one. Here, we developed an in vitro model that mimics a fibrosis-like mechanism using the U-87MG GBM cell line. To achieve this, we identified the optimal experimental conditions (i.e., U-87MG cultured in serum-deprivation medium in the presence of recombinant TGF-B1 at 5 ng/mL for 72 h) that effectively induced fibrosis, as suggested by the counter-regulated expression of E- and N-cadherin and sustained levels of α-SMA and collagen I. As expected, U-87MG fibrotic cells were demonstrated to be more resistant to TMZ (predicted EC₅₀ = 35 µM) as compared to the non-fibrotic counterpart (EC₅₀ not achieved here; predicted EC₅₀ = 351 µM). Accordingly, the anti-fibrotic uPAcyclin—a new derivative cyclic compound inspired as a A6 decapeptide drug—showed a significant cytotoxic effect, sensitizing resistant U-87MG fibrotic cells to TMZ. This highlights that targeting fibrosis may help to overcome TMZ resistance in GBM.