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bioRxiv2026

Aging compromises Zebrafish caudal fin regeneration by disrupting Regenerative gene networks and Cellular metabolism

Zebrafish are widely recognized as a powerful vertebrate model for studying epimorphic regeneration due to their remarkable ability to restore complex tissues. However, regenerative efficiency declines with age, potentially due to alterations in gene regulatory networks and cellular metabolism. In the present study, we investigated the molecular and bioenergetic basis of age-associated regenerative decline by comparing young adult (<1 year) and old adult (>3 years) zebrafish during caudal fin regeneration. To further examine the contribution of mitochondrial function, mitochondrial dysfunction was experimentally induced using rotenone (20 nM), a mitochondrial Complex I inhibitor. Regenerative progression was assessed morphologically at 12hpa, 1dpa, 2dpa, 3dpa, and 7dpa, revealing a pronounced delay in fin regrowth in aged and rotenone-treated fish compared with young controls. Behavioral analysis indicated subtle but non-significant changes across experimental groups. Gene expression analysis using quantitative real-time PCR revealed age- and mitochondria-associated dysregulation of key regenerative gene families involved in developmental patterning, extracellular matrix organization, cellular signaling, and mitochondrial metabolism. Proteomic profiling further identified differential expression of proteins associated with mitochondrial bioenergetics, extracellular matrix remodeling, and signaling pathways required for blastema formation and tissue outgrowth. Ultrastructural examination by transmission electron microscopy revealed pronounced mitochondrial abnormalities, including enlarged mitochondria with fragmented or disrupted cristae, in aged and rotenone-treated regenerating tissues. Collectively, our integrative analysis establishes a mechanistic link between aging, mitochondrial dysfunction, and compromised regenerative capacity in zebrafish. The findings provide broader insights into metabolic constraints underlying age-related decline in regenerative potential in vertebrates.

developmental biology↗

bioRxiv2020

CoalQC - Quality control while inferring demographic histories from genomic data: Application to forest tree genomes

Estimating demographic histories using genomic datasets has proven to be useful in addressing diverse evolutionary questions. Despite improvements in inference methods and availability of large genomic datasets, quality control steps to be performed prior to the use of sequentially Markovian coalescent (SMC) based methods remains understudied. While various filtering and masking steps have been used by previous studies, the rationale for such filtering and its consequences have not been assessed systematically. In this study, we have developed a reusable pipeline called "CoalQC", to investigate potential sources of bias (such as repeat regions, heterogeneous coverage, and callability). First, we demonstrate that genome assembly quality can affect the estimation of demographic history using the genomes of several species. We then use the CoalQC pipeline to evaluate how different repeat classes affect the inference of demographic history in the plant species Populus trichocarpa. Next, we assemble a draft genome by generating whole-genome sequencing data for Mesua ferrea (sampled from Western Ghats, India), a multipurpose forest plant distributed across tropical south-east Asia and use it as an example to evaluate several technical (sequencing technology, PSMC parameter settings) and biological aspects that need to be considered while comparing demographic histories. Finally, we collate the genomic datasets of 14 additional forest tree species to compare the temporal dynamics of Ne and find evidence of a strong bottleneck in all tropical forest plants during Mid-Pleistocene glaciations. Our findings suggest that quality control prior to the use of SMC based methods is important and needs to be standardised.

evolutionary biology↗