Biology subjects

Gerisch, B.

Publications and source records attributed to Gerisch, B..

3 recordsLinked to original sources

bioRxiv2025

Resilience and restoration from fasting-refeeding mediated by a nutrient-regulated linker histone

Intermittent fasting and fasting-refeeding regimens can slow biological aging across taxa1. Shifts between fed and fasted states activate ancient nutrient-sensing pathways which alter cellular and epigenetic states to promote longevity2-4. Yet how biological age trajectories progress during fasting-refeeding, and how nutrient-sensing pathways reprogram epigenetic state remain largely unknown. Here we observe increases in predicted biological age of Caenorhabditis elegans during prolonged fasting in adult reproductive diapause, followed by extraordinary reduction of biological age during refeeding. We identify hil-1/H1-0 as an evolutionarily conserved nutrient-regulated linker histone which mediates adaptations to fasting and refeeding downstream of FOXO and TFEB transcription factors. In C. elegans and human cell culture, hil-1/H1-0 upregulation during low-nutrient states promotes long-term survival and subsequent refeeding-induced recovery. Restoration of C. elegans after prolonged fasting is improved by enhancing the natural downregulation of hil-1 specifically during refeeding. Our study identifies HIL-1/H1.0 as part of an ancestral epigenetic switch during fasting-refeeding that reprograms metabolic and cellular states underlying resilience and restoration.

genetics↗

bioRxiv2023

A primordial TFEB-TGFβ signaling axis systemically regulates diapause and stem cell longevity

Fasting/refeeding enhances animal health and lifespan across taxa. C. elegans can endure months of fasting in adult reproductive diapause (ARD) and upon refeeding, regenerate and reproduce. hlh-30/TFEB is an ARD master regulator whose mutants live mere days in ARD and dont recover with refeeding. Here we find that downregulation of TGF{beta} signaling bypasses hlh-30 collapse, and restores recovery, germline stem cell proliferation and reproductive competence. Upon fasting, HLH-30/TFEB(+) downregulates TGF{beta} in sensory neurons, to inhibit Notch and promote reproductive quiescence in the germline. Upon refeeding, these pathways are upregulated to activate stem cells and promote reproduction. hlh-30 loss induces a senescent-like DNA damage, immune and growth metabolic signature reversed by inhibiting TGF{beta} signaling. TFEBs role is conserved in mammalian diapause models, including mouse embryonic and human cancer diapause. Thus, TFEB-TGF{beta} axis relays systemic signals matching nutrient supply with growth signaling, to regulate stem cell longevity, senescence and regeneration across species.

cell biology↗

bioRxiv2021

miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to affect muscle contractility upon proteotoxic challenge during ageing

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also highly plastic, and remodelled in response to stress, growth, neural and metabolic inputs. The evolutionarily conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle biology during development, but whether it plays a role during ageing is unknown. Here we investigated the role of C. elegans miR-1 in muscle function in response to proteostatic stress during adulthood. mir-1 deletion results in improved mid-life muscle motility, pharyngeal pumping, and organismal longevity under conditions of polyglutamine repeat proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6VIA as a direct target downregulated via its 3UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. In summary, our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during ageing.

genetics↗