Biology subjects

Grundmann, F.

Publications and source records attributed to Grundmann, F..

4 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↗

bioRxiv2024

Approach to standardized material characterization of the human lumbopelvic system - Testing and evaluation

The osseo-ligamentous lumbopelvic complex is a crucial component of the human musculoskeletal system and has been increasingly the focus of medical research and treatment planning. Numerical simulations can play a key role in better understanding the load-carrying behavior of this system, but material data in this arena remain rare. In addition, the literature lacks standardized and reproducible methods for determining biomechanical material parameters. To address these shortcomings, we obtained bone and soft tissue samples from three female and two male cadavers (average age: 77.3 years) for testing and evaluation. The elastic modulus of cortical bone averaged at 1750 MPa with a mean ultimate strength of 28.2 MPa. Whereas for trabecular bone the evaluation yields to 32.7 MPa and 1.26 MPa. Furthermore, the soft tissue specimens exhibited a mean elastic modulus of 148 MPa and an ultimate strength of 14.3 MPa for fascial tissue, in contrast to ligamentous tissue with 103 MPa and 10.7 MPa. Knowledge of these material parameters of the human pelvis, which differ from those of long bones, could, in combination with the revealed dependence on harvesting location and density, lead to more precise mechanical simulations. Such simulations might in turn promote the development of better suited implants. Together with a previous publication dealing with sample preparation, this work is intended to contribute to the standardization of mechanical testing of human tissue. Easy-to-conduct bending tests as well as direct tension and compression tests are recommended, and the proposed mechanical boundary conditions are explained and documented. These technical recommendations allow for better comparability and reproducibility in future biomechanical studies. This protocol, developed for the human pelvis, could easily be transferred to other anatomical regions.

biophysics↗

bioRxiv2021

A systematic analysis of diet-induced nephroprotection reveals overlapping and conserved changes in cysteine catabolism

Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection as well as overlapping metabolic consequences has not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a potential common mechanism of organ protection. Importantly, these metabolic changes can be recapitulated in patients preconditioned by a diet limiting sulfur-containing amino acids indicating conserved diet-induced mechanisms of stress-resistance that may ultimately lead to clinical application.

biochemistry↗

bioRxiv2021

Organ protection by caloric restriction depends on activation of the de novo NAD+ synthesis pathway

Therapeutic strategies to treat acute kidney injury (AKI) are lacking in clinical practice. Interestingly, preconditioning by hypoxia (HP) and caloric restriction (CR) is highly protective in rodent AKI models. However, the underlying molecular mechanisms of this process are unknown. A comparative transcriptome analysis of murine kidneys after HP and CR identified Kynureninase (KYNU) as a common downstream target. Using a newly generated KYNU-deficient mouse line, we show that KYNU strongly contributes to the protective effect of preconditioning. Metabolome, transcriptome and proteome analyses reveal the KYNU-dependent de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway as necessary for CR-associated maintenance of NAD+ levels. Importantly, the impact of CR on the de novo NAD+ biosynthesis pathway can be recapitulated in humans. These findings provide a valuable insight into the molecular mechanisms mediating protection upon preconditioning and point towards the de novo branch of NAD+ biosynthesis as a conserved target in nephroprotection.

physiology↗