Biology subjects

Solari, F.

Publications and source records attributed to Solari, F..

4 recordsLinked to original sources

bioRxiv2026

A nuclear role for the contractile protein troponin I/UNC-27 in regulating muscle aging in C. elegans

Muscle ageing is characterized by evolutionarily conserved subcellular alterations across diverse organisms. In Caenorhabditis elegans, the decline in sarcomeric gene expression is among the earliest detectable ageing-associated changes, emerging at the onset of adulthood. To identify causal regulators of muscle ageing in an unbiased manner, we developed a genetic screening strategy that enables visual monitoring of muscle ageing at both cellular and organismal scales. Using this approach, we identified a mutation that delays the age-associated loss of sarcomeric transcripts. Unexpectedly, the mutation maps to the troponin I gene unc-27, which encodes a conserved regulator of muscle contraction not previously implicated in gene regulation. The mutation alters a single amino acid within a predicted nuclear localization signal (NLS). We found that multiple NLS motifs mediate the active transport of UNC-27 into muscle nuclei from early adulthood onward. Disruption of UNC-27 nuclear localization preserves sarcomeric gene expression during ageing and delays early hallmarks of muscle decline, including proteostatic imbalance and mitochondrial fragmentation. Transcriptomic analyses further revealed that nuclear UNC-27 selectively regulates the expression of genes encoding structural components of the muscle apparatus in adult animals. These results support the existence of a homeostatic sarcomere surveillance pathway, in which a structural protein unexpectedly acquires a transcriptional regulatory role in response to age-associated physiological state. The conservation of NLS motifs in mammalian UNC-27 orthologues suggests that this mechanism may be evolutionarily conserved, with potential relevance to human muscle physiology and disease.

cell biology↗

bioRxiv2026

MOSAIC: a longitudinal phenotypic clock to dissect organismal aging trajectories in C. elegans

Interventions that extend lifespan do not necessarily preserve healthspan, the portion of life spent in good health. This disconnect has intensified interest in biological aging clocks as quantitative proxies of organismal health. However, most existing clocks rely on invasive or endpoint measurements, providing static estimates that capture biological age at a single time point and offer limited insight into aging trajectories - the dynamic patterns through which physiological resilience and functional capacity change within individuals over time. Here we combine standardized, high-frequency imaging of individual Caenorhabditis elegans across the lifespan with machine learning to develop MOSAIC (Modular Organismal Signature of Aging In C. elegans), a non-invasive phenotypic clock that estimates biological age longitudinally at single-organism resolution. Leveraging [~]3750 animals, [~]230000 observations and 29 phenotypic features, MOSAIC predicts biological age with high accuracy and resolves organism-wide aging trajectories at high temporal resolution. Beyond age prediction, MOSAIC decomposes biological age into contributions from distinct physiological modules, enabling mechanistic interpretation of organismal decline. Applying MOSAIC to natural lifespan variation, dietary restriction, longevity mutants and pharmacological interventions reveals that lifespan extension can emerge through distinct, time-dependent phenotypic trajectories rather than a uniform slowing of aging. Interventions with similar effects on longevity produce divergent biological-age trajectories and distinct combinations of younger and older traits, highlighting context-dependent physiological trade-offs. MOSAIC provides a scalable, non-invasive framework to repeatedly quantify biological age across the lifespan and to compare interventions based on how they reshape aging trajectories.

bioinformatics↗

bioRxiv2021

DAF-2/insulin IGF-1 receptor regulates mobility during ageing by integrating opposite inputs from muscle and neuronal tissues

During ageing, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In C. elegans, mutants of the insulin-IGF-1 receptor DAF-2/IIRc represent a paradigm of healthy ageing, as their increased lifespan is accompanied by a delay in age-related loss of motility. However, these animals are less mobile than wild-type animals in early adulthood. Here we investigated the DAF-2/IIRc- dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc. As previously reported, inactivation of DAF-2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2/IIRc prevented the age-related loss of motility. In 1-day-old adults, DAF-2/IIRc depletion in neurons reduced motility in a DAF-16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middleage animals improved their motility independently of DAF-16/FOXO but required UNC-120/SRF. Yet, neuronal or muscle DAF-2/IIRc depletion both preserved the mitochondria network in ageing muscle. Overall, these results show that the motility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.

physiology↗

bioRxiv2019

Near-optimal combination of disparity across a log-polar scaled visual field

The human visual system is foveated: we can see fine spatial details in central vision, whereas resolution is poor in our peripheral visual field, and this loss of resolution follows an approximately logarithmic decrease. Additionally, our brain organizes visual input in polar coordinates. Therefore, the image projection occurring between retina and primary visual cortex can be mathematically described by the log-polar transform. Here, we test and model how this space-variant visual processing affects how we process binocular disparity, a key component of human depth perception. We observe that the fovea preferentially processes disparities at fine spatial scales, whereas the visual periphery is tuned for coarse spatial scales, in line with the naturally occurring distributions of depths and disparities in the real-world. We further show that the visual field integrates disparity information across the visual field, in a near-optimal fashion. We develop a foveated, log-polar model that mimics the processing of depth information in primary visual cortex and that can process disparity directly in the cortical domain representation. This model takes real images as input and recreates the observed topography of disparity sensitivity in man. Our findings support the notion that our foveated, binocular visual system has been moulded by the statistics of our visual environment.\n\nAuthor summaryWe investigate how humans perceive depth from binocular disparity at different spatial scales and across different regions of the visual field. We show that small changes in disparity-defined depth are detected best in central vision, whereas peripheral vision best captures the coarser structure of the environment. We also demonstrate that depth information extracted from different regions of the visual field is combined into a unified depth percept. We then construct an image-computable model of disparity processing that takes into account how our brain organizes the visual input at our retinae. The model operates directly in cortical image space, and neatly accounts for human depth perception across the visual field.

neuroscience↗