Finasteride linked to shorter lifespan and motor deficits in fly study

Finasteride is one of the most widely prescribed drugs in men’s health, taken by millions to shrink enlarged prostates and slow hair loss by blocking the conversion of testosterone into the more potent androgen dihydrotestosterone. A new study in the journal Biogerontology suggests that this blockbuster medication may carry biological costs that have little to do with its androgen targets. Using fruit flies as the primary model and a mouse behavioral assay as a complementary approach, researchers in China found that Finasteride exposure was associated with shortened lifespan, elevated reactive oxygen species in the gut, impaired movement, and structural changes at the neuromuscular junction, the synapse where motor neurons command muscle fibers. The work, led by Keyao Long, Keyi Mo, and colleagues in the laboratory of Menglong Rui at Southeast University in Nanjing, also pinpointed a candidate molecular player: cask, a gene whose expression dropped in exposed flies and whose restoration in motor neurons partially rescued the drug’s effects on synapse architecture and locomotion.

The findings arrive amid a growing and often heated debate over Finasteride’s side-effect profile. Clinicians have long documented sexual dysfunction, depression, and, in a subset of former users, a constellation of persistent symptoms described as post-finasteride syndrome. Large database analyses have even linked the drug to increased risks of suicidality and depression, and rodent studies have shown that Finasteride can inhibit the brain’s dopaminergic system and blunt responses to both stressful and rewarding stimuli. What has been missing is a systematic, whole-organism view of how the drug affects aging biology, from lifespan to the motor circuits that deteriorate in conditions like Parkinson’s disease. The new study attempts to supply exactly that, treating Finasteride not merely as an androgen modulator but as a compound with potentially pervasive developmental and neuronal effects.

The experimental logic of the work rests on Drosophila melanogaster, the fruit fly that has anchored genetics and aging research for more than a century. Flies offer a uniquely tractable system for dissecting drug effects: their lifespan can be measured precisely across thousands of individuals, their neuromuscular junctions are large and accessible for morphological analysis, and their genome can be manipulated with surgical ease. The researchers combined developmental and behavioral assessments with morphological analyses of motor and sensory neurons, transcriptomics to survey genome-wide changes in gene expression, and genetic methods to test candidate mechanisms. A mouse behavioral assay served as a complementary approach, acknowledging that no single model can capture the full biology of a drug designed for human physiology.

The lifespan results were unambiguous. Finasteride exposure was associated with shortened lifespan in both male and female flies, indicating that the drug’s effects on longevity are not confined to one sex. Alongside this reduction in survival, the team observed increased accumulation of reactive oxygen species, or ROS, in the intestine. This detail matters because the fly gut is a well-established sentinel of aging: oxidative damage in intestinal tissue is tightly linked to mortality in Drosophila, and interventions that curb gut ROS, from dietary restriction to antioxidant compounds, reliably extend lifespan. The association between Finasteride exposure and intestinal oxidative stress therefore offers a plausible mechanistic thread connecting the drug to shortened survival, though the study stops short of proving causation.

Not every effect was symmetrical across the sexes. Finasteride exposure significantly reduced starvation resistance in male flies but not in females, a sex-dependent vulnerability that echoes a broader theme in Drosophila aging research. Starvation resistance, the ability to survive prolonged food deprivation, depends on metabolic reserves, hormonal state, and behavior, and recent work has shown pervasive sex-dependent effects in the genetic architecture of this trait. Given that Finasteride’s primary clinical action is to deplete dihydrotestosterone, an androgen with documented roles in metabolism and behavior, the male-specific metabolic fragility observed in flies raises questions about whether androgen signaling shapes stress resilience in ways the drug inadvertently disrupts.

The behavioral and neuronal findings point in a consistent direction. Flies exposed to Finasteride showed reduced locomotor performance, a deficit that matters because declining movement is one of the most reliable predictors of mortality and cognitive decline in aging populations, from handgrip strength in humans to climbing speed in flies. When the researchers examined the neuromuscular junction, the synapse where motor neurons interface with muscle, they found altered morphology in exposed animals. Structural integrity at this synapse is essential for synaptic transmission, and its disruption is a hallmark of Drosophila models of neurodegenerative disease, including ALS-like conditions caused by mutant FUS protein. The team also analyzed class IV dendritic arborization sensory neurons, the elaborate somatosensory neurons that the same laboratory has studied for years in the context of neurite remodeling, surveying whether the drug perturbs the development or maintenance of these arborizing dendritic fields.

Transcriptomics supplied the molecular clue. Gene expression profiling revealed decreased expression of cask in Finasteride-exposed flies. CASK is no peripheral player: in Drosophila, this conserved scaffolding protein, which exists in isoforms containing CaMK-like and L27 domains, is central to locomotor behavior, and genetic interaction between CASK’s partners at the neuromuscular junction is important for synaptic function. In humans, CASK mutations cause MICPCH syndrome, a severe X-linked neurodevelopmental disorder, and recent mouse studies have shown that CASK deficiency kills cerebellar granule cells in models of that disease. The convergence of the drug exposure phenotype with this well-characterized neurodevelopmental gene gave the researchers a concrete hypothesis to test.

The genetic rescue experiment delivered the study’s most striking result. When the team drove overexpression of CASK specifically in motor neurons of Finasteride-exposed flies, the drug-associated damage partially reversed: neuromuscular junction morphology improved, and locomotor performance recovered. This rescue demonstrates that the drug’s effects on the motor synapse are not irreversible structural destruction but a perturbation of a gene regulatory state that neurons can restore when given sufficient CASK. It also elevates cask from a correlational transcriptomic hit to a candidate mechanistic mediator, one whose expression the drug suppresses and whose restoration counteracts the synaptic and behavioral consequences of exposure.

The authors are careful about the boundaries of their claims. The study reveals changes in lifespan and locomotor phenotypes associated with Finasteride exposure and highlights the importance of investigating the drug’s broader biological effects in other experimental systems, but it does not claim that Finasteride causes equivalent harm in humans at therapeutic doses. Flies received defined exposures under controlled conditions, and the dose, timing, and metabolic context of drug delivery in Drosophila differ substantially from oral Finasteride therapy in men. The mouse behavioral assay provides a complementary mammalian data point, but translating synaptic morphology and oxidative stress findings across species requires the very follow-up work the study calls for, in mammalian models and ultimately in clinical cohorts.

Even with those caveats, the study lands at a moment when the scientific community is rethinking how thoroughly drugs like Finasteride have been vetted for effects beyond their primary indications. The drug inhibits 5α-reductase, the enzyme family that converts testosterone to dihydrotestosterone, and its structural interaction with the 5α-reductase 2 enzyme has been solved in detail, yet the downstream consequences of androgen depletion ripple through neurosteroid synthesis, stress responses, and brain development in ways that are still being mapped. If a compound prescribed for prostate enlargement and hair loss shortens lifespan and perturbs motor synapses in a model organism, the prudent response is not alarm but expanded scrutiny: rigorous testing of the drug’s effects on aging, metabolism, and the nervous system across experimental systems, with particular attention to the patients, often young and healthy men taking it for cosmetic reasons, who have the longest exposure horizons. The Southeast University team’s work provides a template for that scrutiny, combining lifespan assays, behavioral testing, synaptic anatomy, transcriptomics, and genetic rescue into a single coherent investigative arc, and identifying a concrete molecular target, CASK, around which future studies in mammals and humans can organize.

Subject of Research: Effects of Finasteride exposure on lifespan and locomotor phenotypes

Article Title: Effects of Finasteride exposure on lifespan and locomotor phenotypes

Article References: Long, K., Mo, K., Xu, K., Yang, X., Xu, X., Wang, S., & Rui, M. (2026). Effects of Finasteride exposure on lifespan and locomotor phenotypes. Biogerontology, 27(6), Article 181. https://doi.org/10.1007/s10522-026-10529-7

Image Credits: AI Generated

DOI: 10.1007/s10522-026-10529-7

Keywords: Effects, Finasteride, exposure, lifespan, locomotor, phenotypes, scientific research