Events Calendar

Environmental and Occupational Health Sciences Journal Club

EOH student Zachary Clemens will present the article:

The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function

Zachary Clemens, Sruthi Sivakumar, Abish Pius, Amrita Sahu, Sunita Shinde, Hikaru Mamiya, Nathaniel Luketich, Jian Cui, Purushottam Dixit, Joerg D Hoeck, Sebastian Kreuz, Michael Franti, Aaron Barchowsky, Fabrisia Ambrosio

Abstract: Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing ‘disorderliness’ of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular ‘order’ and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.sues. Although the magnitude of transcriptional change detected with PM2.5 exposure was lower than that observed with a HFD, the degree of alteration in chromatin accessibility after PM2.5 exposure was significant. The novel chromatin remodeler SMARCA5 (SWI/SNF complex) was regulated in response to PM2.5 exposure, the cessation of which was associated with a reversal of insulin resistance and restoration of chromatin accessibility and nucleosome positioning near transcription start sites, as well as a reversal of exposure-induced changes in the transcriptome, including SMARCA5. These changes indicate pliable epigenetic control mechanisms following cessation of exposure.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Thursday, September 16 at 11:00 a.m. to 12:00 p.m.

Public Health, A215
130 Desoto Street, Pittsburgh, 15261

Environmental and Occupational Health Sciences Journal Club

EOH student Zachary Clemens will present the article:

The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function

Zachary Clemens, Sruthi Sivakumar, Abish Pius, Amrita Sahu, Sunita Shinde, Hikaru Mamiya, Nathaniel Luketich, Jian Cui, Purushottam Dixit, Joerg D Hoeck, Sebastian Kreuz, Michael Franti, Aaron Barchowsky, Fabrisia Ambrosio

Abstract: Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing ‘disorderliness’ of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular ‘order’ and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.sues. Although the magnitude of transcriptional change detected with PM2.5 exposure was lower than that observed with a HFD, the degree of alteration in chromatin accessibility after PM2.5 exposure was significant. The novel chromatin remodeler SMARCA5 (SWI/SNF complex) was regulated in response to PM2.5 exposure, the cessation of which was associated with a reversal of insulin resistance and restoration of chromatin accessibility and nucleosome positioning near transcription start sites, as well as a reversal of exposure-induced changes in the transcriptome, including SMARCA5. These changes indicate pliable epigenetic control mechanisms following cessation of exposure.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.

Thursday, September 16 at 11:00 a.m. to 12:00 p.m.

Public Health, A215
130 Desoto Street, Pittsburgh, 15261

Event Type

Virtual

Topic

Research

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