
Alexander M WolfInstitute for Globally Distributed Open Research and Education (IGDORE) | IGDORE
Alexander M Wolf
PhD
My primary interest is the molecular mechanism(s) driving human aging.
About
24
Publications
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Introduction
I work on the molecular mechanisms driving human aging
Additional affiliations
October 2018 - May 2021
September 2006 - September 2018
January 2006 - August 2006
Education
April 2000 - June 2002
April 1999 - October 2004
Publications
Publications (24)
Background:
Oxidative stress is involved in the progression of diabetes and its associated complications. However, it is unclear whether increased oxidative stress plays a primary role in the onset of diabetes or is a secondary indicator caused by tissue damage. Previous methods of analyzing oxidative stress have involved measuring the changes in...
Despite continued increases in human life expectancy, the factors determining the rate of human biological aging remain unknown. Without understanding the molecular mechanisms underlying aging, efforts to prevent aging are unlikely to succeed. The tumor suppression theory of aging introduced here proposes somatic mutation as the proximal cause of a...
Understanding the molecular mechanisms of normal aging is a prerequisite to significantly improving human health span. Caloric restriction (CR) can delay aging and has served as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity. Health gains from CR depend on control mice b...
Understanding the molecular mechanisms of normal aging is a prerequisite to significantly increase human health span. Caloric restriction (CR), which delays aging in most animal models, serves as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity and benefits from CR might b...
Immune checkpoint inhibitors are causing a paradigm shift in cancer treatment. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dampen T cell activation to avoid autoimmunity and the destructive effects of an excessive inflammatory response. Immune checkpoint signali...
Oxidative stress and reactive oxygen species (ROS) are signaling factors thought to be important drivers of ageing due to their unique ability to damage DNA, as aging and cancer are driven by the accumulation of mutations in stem cells of proliferative tissue. They are an attractive target for interventions, but the development of such intervention...
Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing red...
München, Techn. Univ., Diss., 2004.
Oxidative stress is involved in many age-associated diseases, as well as in the aging process itself. The development of interventions to reduce oxidative stress is hampered by the absence of sensitive detection methods that can be used in live animals. We generated transgenic mice expressing ratiometric redox-sensitive green fluorescent protein (r...
Measles virus (MV) is known for its ability to cause an acute infection with a potential of development of persistent infection. However, knowledge of how viral genes and cellular factors interact to cause or maintain the persistent infection has remained unclear. We have previously reported the possible involvement of mitochondrial short chain eno...
Objective:
Post-transcriptional taurine modification at the first anticodon ("wobble") nucleotide is deficient in A3243G-mutant mitochondrial (mt) tRNA(Leu(UUR)) of patients with myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Wobble nucleotide modifications in tRNAs have recently been identified to be important in the...
Caloric restriction (CR) confers cardioprotection against ischemia/reperfusion injury. However, the exact mechanism(s) underlying CR-induced cardioprotection remain(s) unknown. Recent evidence indicates that Sirtuins, NAD(+)-dependent deacetylases, regulate various favorable aspects of the CR response. Thus, we hypothesized that deacetylation of sp...
Somatic mutations of mitochondrial DNA (mtDNA) have been reported in different types of cancers and are suggested to play roles in metastasis, cancer development and response to anticancer agents. To predict potential roles of mtDNA alterations in colorectal cancer, we determined the entire mtDNA sequence of eleven human-derived colorectal cancer c...
Mutations in PTEN-induced putative kinase 1 (PINK1) cause a recessive form of Parkinson's disease (PD). PINK1 is associated with mitochondrial quality control and its partial knock-down induces mitochondrial dysfunction including decreased membrane potential and increased vulnerability against mitochondrial toxins, but the exact function of PINK1 i...
Aldehyde accumulation is regarded as a pathognomonic feature of oxidative stress-associated cardiovascular disease.
We investigated how the heart compensates for the accelerated accumulation of aldehydes.
Aldehyde dehydrogenase 2 (ALDH2) has a major role in aldehyde detoxification in the mitochondria, a major source of aldehydes. Transgenic (Tg) mi...
Mitochondria combine the production of energy with an efficient chain of reduction-oxidation (redox) reactions but also with the unavoidable production of reactive oxygen species. Oxidative stress leading to mitochondrial dysfunction is a critical factor in many diseases, such as cancer and neurodegenerative and lifestyle-related diseases. Effectiv...
Redox-sensitive green fluorescent protein (roGFP) is a fluorescent protein in which two cysteines are placed adjacently in the barrel structure. Disulfide formation (oxidation) increases the absorption at short wavelengths (410 nm) at the expense of absorption at longer wavelengths (490 nm). The fluorescence ratio indicates reduction/oxidation, i.e...
Micelacking both Kv3.1 and both Kv3.3 K+ channel alleles display severe motor deficits such as tremor, myoclonus, and ataxic gait. Micelacking one to three alleles at the Kv3.1 and Kv3.3 loci exhibit in an allele dose-dependent manner a modest degree of ataxia. Cerebellar granule cells coexpress Kv3.1 and Kv3.3 K+ channels and are therefore candida...
Optical recording of neuronal activities using voltage-sensitive dyes (VSDs) is a useful method for simultaneous multi-site recording. However, it has been rather difficult to distinguish optical signals from individual, identified cells. We applied the optical recording technique using a high-speed charge coupled device (CCD) imaging system to a t...
In the rodent primary somatosensory cortex, the configuration of whiskers and sinus hairs on the snout and of receptor-dense zones on the paws is topographically represented as discrete modules of layer IV granule cells (barrels) and thalamocortical afferent terminals. The role of neural activity, particularly activity mediated by NMDARs (N-methyl-...
Questions
Questions (2)
I am looking for a mouse line in which (CD8+) cytotoxic T cells (CTLs) are marked by expression of a fluorescent protein. Red fluorescent proteins would be best, but (E)GFP or any other fluorescent protein is also ok. Both transgenic or a Cre reporter strain-based approach would be fine. Precise specificity for CTLs is not a requirements, but the marked cells should include CTLs.
I want to use these mice in vivo and therefore it would be great if there would be pictures showing fluorescent protein expression in vivo.
Is force strictly determined by muscle cell calcium alone? Can the same muscle force be achieved with different intracellular calcium concentrations? I don't mean long term changes in muscle structure, of course. For example, dantrolene reduces calcium efflux from the sarcoplasmic reticulum and reduces grip strength in mice. Does a 20% reduction in peak force mean a 20% reduction in intracellular peak calcium? Can the same force be achieved with different calcium concentrations? If there are other factors, what are they? Can anyone recommend an article discussing such quantitative aspects?