Biomedical subjects

Donald A Jurivich

Publications and source records attributed to Donald A Jurivich.

3 recordsLinked to original sources

PubMed2007

Pathomolecular effects of homocysteine on the aging process: a new theory of aging.

Homocysteine has been associated with the most common age-related diseases but never associated with the acceleration of the aging process. This theoretical paper will try to demonstrate the pro-aging effects of homocysteine at the molecular, cellular, and organ level. High homocysteine levels in homocystinuria are associated with premature disease of the cardiovascular, skeletal, neurological, and other systems. These observations are similar to those noted in the aging process and should be considered as a progeroid syndrome. There is enough scientific evidence to support that homocysteine accelerates the aging process at the cellular and at the organism level. Most importantly, decreasing homocysteine levels by dietary or pharmacological interventions could prolong maximum life span in humans and/or delay the onset of the most common age-related diseases.

Aging↗

PubMed2006

Clonal senescence alters endothelial ICAM-1 function.

Little is known how age alters the dynamics and function of cell adhesion molecules, especially under inflammatory and stressful conditions. One membrane constituent, intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein of the immunoglobulin (Ig) superfamily that regulates key outside-->in and inside-->out signals associated with cell-to-cell interactions. If conditions such as age and inflammation change usual ICAM-1 action then important downstream effects ultimately perturb endothelial cell function. In this report, ICAM-1 accumulates in late passage endothelial cells when compared to early passage endothelial cells, yet ICAM-1 protein expression is attenuated when senescent cells are challenged by TNF-alpha (10ng/ml). Importantly, age alters ICAM-1 dynamic properties from directed to random receptor motion within the membrane. Single particle tracking reveals that the average ICAM-1 mobility is 44% less in late than early passage cells after its motion is stimulated by the Protein Kinase C (PKC) activator, phorbol myristate acetate (PMA). The mechanism for altered ICAM-1 mobility partly can be explained by a reduced rate of alpha-actinin linking with ICAM-1 in late passage Human Pulmonary Artery Endothelial Cells (HPAECs). Furthermore, tyrosine phosphorylation of alpha-actinin, a requirment for ICAM-1 clustering, is markedly reduced in senescent cells. These findings support a hypothesis that senescence results in changes of ICAM-1 activation and clustering, thus resulting in an age-dependent transmembrane signaling disorder. Therefore, further understanding of age-dependent disturbances of ICAM-1 regulation during inflammation can provide important clues as to appropriate targets for therapeutic interventions and prevention of vascular disorders in elderly at the level of the endothelial surface membrane.

Actinin↗

PubMed2005

Human aging alters the first phase of the molecular response to stress in T-cells.

This study examines how age affects the first phase of the heat shock response in human T-cells. To understand how age alters transcriptional regulation of the heat shock genes, a cross-sectional study was conducted utilizing human T-cells enriched from peripheral blood lymphocytes of healthy young (20-40 years old) and old (>70 years old) donors. Nuclear run-on analysis revealed a 66% reduction in hsp70 transcription rates in old compared to young nuclei harvested from T-cells exposed to a brief 42 degrees C heat shock. To determine if one or more protein transactivators of the proximal and distal promoter regions of the hsp70 gene were affected by age, gel shift analysis was performed. Both HSF1 and SP1 DNA-binding were reduced with age but no reduction was noted in CCAAT-DNA binding. Western blot analysis indicated that HSF1 but not HSF2 protein levels were reduced in aged donor samples. These data suggest that human T-cell senescence involves a multi-factorial mechanism that diminishes an important transcriptional response to thermal stress. The results are discussed relative to recent studies that support a multi-factorial mechanism for age-dependent attenuation of the heat shock transcription factor.

Adult↗