Sebastian J. Hofer

Sebastian J. Hofer
French Institute of Health and Medical Research | Inserm · U1138

Dr. rer. nat.

About

41
Publications
17,691
Reads
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1,135
Citations
Introduction
Sebastian Hofer is a postdoctoral researcher at the Institute of Molecular Biosciences in Graz, Austria. He focuses on improving our understanding of anti-aging interventions and tries to accelerate their translation to clinical application. In-between steps include research on yeast, flies and mice. His main interests are polyamines, autophagy, mitochondria and (intermittent) fasting / caloric restriction.
Additional affiliations
October 2019 - present
Karl-Franzens-Universität Graz
Position
  • PostDoc Position
January 2017 - October 2019
Karl-Franzens-Universität Graz
Position
  • PhD Student
July 2016 - December 2016
Freie Universität Berlin
Position
  • Visiting researcher
Education
March 2014 - May 2016
Graz University of Technology
Field of study
  • Molecular Microbiology
October 2010 - March 2014
Graz University of Technology
Field of study
  • Molecular Biology

Publications

Publications (41)
Article
The increase in life expectancy has boosted the incidence of age-related pathologies beyond social and economic sustainability. Consequently, there is an urgent need for interventions that revert or at least prevent the pathogenic age-associated deterioration. The permanent or periodic reduction of calorie intake without malnutrition (caloric restr...
Article
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy,...
Article
Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type–spec...
Article
Full-text available
Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan- extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that die- tary spermidine passes the bloo...
Chapter
Numerous pro-autophagic dietary interventions are being investigated for their potential cancer-preventive or therapeutic effects. This applies to different fasting regimens, methionine restriction and ketogenic diets. In addition, the supplementation of specific micronutrients such as nicotinamide (vitamin B3) or spermidine induces autophagy. In h...
Article
Importance: Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvemen...
Article
Background: The insulin/insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial. Methods: We performed a lifelong study to assess cardiac health and lifespan in 2 cardi...
Article
Full-text available
Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer's disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yea...
Article
Viral, bacterial, fungal and protozoal biology is of cardinal importance for the evolutionary history of life, ecology, biotechnology and infectious diseases. Various microbiological model systems have fundamentally contributed to the understanding of molecular and cellular processes, including the cell cycle, cell death, mitochondrial biogenesis,...
Article
Subjective Cognitive Decline (SCD) may represent an early, pre‐clinical manifestation of Alzheimer’s disease (Jessen et al., 2014), possibly accompanied by detrimental changes in white matter (WM) microstructure (Brueggen et al., 2019). Neuroprotective effects of increased external supply of spermidine were demonstrated in aged animal models (Madeo...
Article
Full-text available
Age-associated diseases are rising to pandemic proportions, exposing the need for efficient and low-cost methods to tackle these maladies at symptomatic, behavioral, metabolic, and physiological levels. While nutrition and health are closely intertwined, our limited understanding of how diet precisely influences disease often precludes the medical...
Article
Full-text available
The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and...
Article
Full-text available
Spermidine is a natural polyamine, central to cellular homeostasis and growth, that promotes macroautophagy/autophagy. The polyamine pathway is highly conserved from bacteria to mammals and spermidine (prominently found in some kinds of aged cheese, wheat germs, nuts, soybeans, and fermented products thereof, among others) is an intrinsic part of t...
Article
Full-text available
Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD ⁺ ). Elevating NAD ⁺ by oral supple...
Article
Full-text available
Ageing provokes a plethora of molecular, cellular and physiological deteriorations, including heart failure, neurodegeneration, metabolic maladaptation, telomere attrition and hair loss. Interestingly, on the molecular level, the capacity to induce autophagy, a cellular recycling and cleaning process, declines with age across a large spectrum of mo...
Article
Full-text available
Autophagy is a catabolic pathway with multifaceted roles in cellular homeostasis. This process is also involved in the antiviral response at multiple levels, including the direct elimination of intruding viruses (virophagy), the presentation of viral antigens, the fitness of immune cells, and the inhibition of excessive inflammatory reactions. In l...
Chapter
Unicellular organisms like yeast can undergo controlled demise in a manner that is partly reminiscent of mammalian cell death. This is true at the levels of both mechanistic and functional conservation. Yeast offers the combination of unparalleled genetic amenability and a comparatively simple biology to understand both the regulation and evolution...
Article
Full-text available
Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila....
Article
Full-text available
Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3...
Article
Full-text available
The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age-related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longev...
Article
Full-text available
Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-coenzyme A carboxylase 1 (Acc1) connects central energy- to lipid metabolism and is rate limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences a...
Article
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GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced acti...
Article
Full-text available
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC...
Article
Full-text available
Huntington's disease (HD) is a neurodegenerative disorder that leads to progressive neuronal loss, provoking impaired motor control, cognitive decline, and dementia. So far, HD remains incurable, and available drugs are effective only for symptomatic management. HD is caused by a mutant form of the huntingtin protein, which harbors an elongated pol...
Article
Full-text available
In the search for interventions against aging and age-related diseases, biological screening platforms are indispensable tools to identify anti-aging compounds among large substance libraries. The budding yeast, Saccharomyces cerevisiae, has emerged as a powerful chemical and genetic screening platform, as it combines a rapid workflow with experime...
Article
Full-text available
Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing....
Article
Full-text available
Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing....
Article
Full-text available
The recent announcement of the 2016 Nobel Prize in Physiology or Medicine, awarded to Yoshinori Ohsumi for the discoveries of mechanisms governing autophagy, underscores the importance of intracellular degradation and recycling. At the same time, it further cements yeast, in which this field decisively developed, as a prolific model organism. Here...

Questions

Questions (2)
Question
Accordingly MitoTracker is commonly used for staining mitochondria in fixed cells. Did anyone try it on specific tissue, such as brains of Drosophila? Did it work? If so, how did you proceed?
I'm also interested in any problems you encountered with MitoTracker-based whole organ staining! Thanks for helping.
Appreciating any feedback,
Sebastian
Question
We want to study mitochondrial health in Drosophila, e.g. by JC-1 or TMRE staining of the MMP. Can somebody recommend a specific dye for fluorescence microscopy or a different approach to do so in specific Drosophila tissue (brain, muscle, heart)?
We'd appreciate any feedback!

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