How cells that refuse to die are slowly turning lungs to scar tissue
Pulmonary fibrosis is one of the most devastating age-related diseases — the lungs stiffen progressively, with no effective cure.
Researchers have mapped in greater detail the role of a protein called BCL-2 in pulmonary fibrosis. BCL-2 is a pro-survival protein: it prevents cells from undergoing controlled cell death, a process called apoptosis. Under normal circumstances, that is useful. But senescent cells — cells that are damaged and should die — exploit BCL-2 to stay alive. They accumulate in lung tissue, secrete pro-inflammatory substances, and activate fibroblasts, the cells responsible for producing scar tissue. The result is progressive pulmonary fibrosis: the lung loses elasticity, oxygen transfer deteriorates, and patients gradually lose respiratory capacity.
The first generation of senolytics — drugs designed to kill senescent cells — works partly through BCL-2 inhibition. Dasatinib and navitoclax, two of the most studied candidates, block BCL-2 and related proteins. An early clinical trial in pulmonary fibrosis patients produced encouraging results. But development has since stalled: pulmonary fibrosis receives relatively little attention from companies developing newer senolytics, partly because of the difficult investment environment of recent years.
A mechanistic window into a disease that remains largely untreatable
What this research adds is a more detailed understanding of how BCL-2 specifically contributes to the disease — not only as a survival mechanism for senescent cells, but as a signalling player within the broader fibrotic network. That has implications for selecting therapeutic targets. BCL-2 inhibitors are already approved for other conditions, including certain forms of leukaemia. The pharmacology exists. The question is whether applying it to pulmonary fibrosis is feasible without unacceptable side effects elsewhere in the body.
Pulmonary fibrosis predominantly affects people over sixty and carries a median survival of three to five years after diagnosis — worse than many cancers. The current standard of care slows progression somewhat but does not reverse it. Senolytics remain the only drug class that, in principle, could target the underlying cause — the accumulation of senescent cells — rather than managing symptoms. Whether that translates into clinical benefit, and in which patients, is what future trials need to establish.
In the meantime, pulmonary fibrosis remains a disease where mechanistic understanding is advancing faster than therapeutic translation — a pattern that is, unfortunately, not unusual in longevity medicine.