Biology subjects

Cameron-Pack, M.

Publications and source records attributed to Cameron-Pack, M..

3 recordsLinked to original sources

bioRxiv2026

Strong inhibition of insulin/IGF-1 signaling in early-mid adulthood compresses morbidity, but in later life accelerates aging

Reduced insulin/IGF-1 signaling (IIS) can greatly extend lifespan in C. elegans. However, its effects on the duration of healthy life (healthspan) remain unclear, with several reports of either morbidity expansion or scaled effects, though none of morbidity compression. Moreover, life-extension by IIS reduction is particularly inter-individually variable within populations, confounding efforts to understand the intra-individual biology of such interventions. Here, we performed a longitudinal investigation at individual nematode resolution, of IIS reduction on aging-related health and lifespan, through temporally-controlled auxin-induced degradation (AID) of the DAF-2 insulin/IGF-1 receptor. Our results show how inter-individual variation in aging rate within control populations explains the complex demographic effects of age-specific DAF-2 AID on population lifespan. Strikingly, adult-limited IIS reduction causes an inter-individually homogeneous increase in lifespan (reducing Gompertz rather than {beta}) that is driven by healthspan expansion and compression of morbidity. Unexpectedly, cessation of DAF-2 AID in decrepit elderly individuals rejuvenates locomotory capacity and extends lifespan, showing that higher levels of IIS are optimal for health and survival towards the end of life. We also document a memory effect of transient IIS reduction during early adulthood, that is sufficient to fully extend lifespan (+189% median lifespan). Together, these findings demonstrate that both lifespan and healthspan can be maximized by appropriate temporal and directional modulation of IIS.

genetics↗

bioRxiv2025

Gelatinase activity is required for Muller glia morphogenesis and neuronal maintenance in the retina

Glial cells are indispensable support elements of the nervous system, yet the mechanisms by which they integrate into densely packed, extracellular matrix (ECM)-rich cellular environments remain poorly understood. In the retina, Muller glia (MG) serve as the principal support cells, performing roles analogous to astrocytes in the brain. As late-born retinal cells, MG undergo morphogenesis within a complex extracellular milieu composed of neighbouring neurons, synapses, and ECM components. Using the zebrafish retina, we show that developing MG dynamically interact with the ECM across all retinal layers while expressing the ECM-remodelling enzymes matrix metalloproteinases (Mmp) 2 and 9. Although Mmps are known to contribute to tissue remodelling and disease processes such as glioma invasion, their developmental roles in glia remain less defined. Here, we demonstrate that Mmp2 and Mmp9 are required for MG morphogenesis and glia-neuron integration. Pharmacological inhibition or genetic loss of mmp2 and mmp9 impaired MG outgrowth and reduced process complexity within synaptic layers, leading to decreased MG-synapse associations. Double mutants (mmp2-/-;mmp9-/-) displayed normal neuronal development and visual function at larval stages but exhibited gliosis, premature neurodegeneration, and visual deficits in adulthood. Together, these findings reveal that Mmp2 and Mmp9 are critical for establishing MG-synapse interactions during development and for maintaining neuronal integrity and visual function in the mature retina.

neuroscience↗

bioRxiv2022

Alone in a crowd: Effect of a nonfunctional lateral line on expression of the social hormone parathyroid hormone 2.

Parathyroid hormone 2 (Pth2) is a vertebrate-specific neuropeptide whose thalamic expression is upregulated by social contact with conspecifics. However, social interactions fail to stimulate pth2 expression in isolated zebrafish whose lateral line hair cells have been chemically ablated. These results suggest that modulation of pth2 by social context is acutely dependent on mechanosensory information from the lateral line. However, it is unclear how a congenital loss of lateral line function influences the ability of zebrafish to interpret their social environment. In this study, we measure pth2 levels in zebrafish mutants lacking hair cell function in either the lateral line only, or in both the inner ear and lateral line. Socially-raised lateral line mutants express lower levels of pth2 relative to wild type siblings, but there is no further reduction when all sensory hair cells are nonfunctional. However, social isolation of hair cell mutants causes a further reduction in pth2 expression, pointing to additional unidentified sensory cues that influence pth2 production. Lastly, we report that social context modulates fluorescent transgenes driven by the pth2 promoter. Altogether, these data suggest that lateral line mutants experience a form of isolation, even when raised in a social environment. SUMMARY STATEMENTExpression of the pro-social neuropeptide pth2 is downregulated in larval zebrafish with a congenital loss of lateral line function. Thus, even in social environments, fish with compromised lateral lines may experience a form of isolation.

neuroscience↗