The Fourth Annual Symposium of the Midwest Aging Consortium.

The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023.

Sirt6 regulates lifespan in .

Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. are an excellent model to study genetic regulation of lifespan; however, despite extensive study in mammals, very little is known about Sirt6 function in flies.

Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells.

The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficult-to-transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake.

DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations With Cigarette Smoking and Subclinical Atherosclerosis.

Background: Tobacco smoke contains numerous agonists of the aryl hydrocarbon receptor (AhR) pathway, and activation of the AhR pathway was shown to promote atherosclerosis in mice. Intriguingly, cigarette smoking is most strongly and robustly associated with DNA modifications to an AhR pathway gene, the AhR repressor (AHRR). We hypothesized that altered AHRR methylation in monocytes, a cell type sensitive to cigarette smoking and involved in atherogenesis, may be a part of the biological link between cigarette smoking and atherosclerosis.

Transcriptomic profiles of aging in purified human immune cells.

Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret.

Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR ≤ 0.

Age-related variations in the methylome associated with gene expression in human monocytes and T cells.

Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes.

Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells.

Escape from cellular senescence induction is a potent mechanism for chemoresistance. Cellular senescence can be induced in breast cancer cell lines by the removal of estrogen signaling with tamoxifen or by the accumulation of DNA damage induced by the chemotherapeutic drug doxorubicin. Long term culturing of the hormone-sensitive breast cancer cell line MCF-7 in doxorubicin (MCF-7/DoxR) reduced the ability of doxorubicin, but not tamoxifen, to induce senescence.

Increased CaVbeta1A expression with aging contributes to skeletal muscle weakness.

Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. Excitation-contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation-contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel alpha1s (CaV1.

Alteration of Akt activity increases chemotherapeutic drug and hormonal resistance in breast cancer yet confers an achilles heel by sensitization to targeted therapy.

The PI3K/PTEN/Akt/mTOR pathway plays critical roles in the regulation of cell growth. The effects of this pathway on drug resistance and cellular senescence of breast cancer cells has been a focus of our laboratory. Introduction of activated Akt or mutant PTEN constructs which lack lipid phosphatase [PTEN(G129E)] or lipid and protein phosphatase [PTEN(C124S)] activity increased the resistance of the cells to the chemotherapeutic drug doxorubicin, and the hormonal drug tamoxifen.