Lemuel M Gitari | Seattle University (original) (raw)

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Papers by Lemuel M Gitari

Ageing Research Reviews, Sep 1, 2015

Aging cell, Aug 8, 2016

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with agi... more Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with aging and a broad spectrum of pathologies. We have previously shown that transgenic expression of the antioxidant enzyme catalase targeted to the mitochondria (mCAT) in mice reduces ROS, attenuates age-related disease, and increases lifespan. However, it has been increasingly recognized that ROS also has beneficial roles in signaling, hormesis, stress response, and immunity. We therefore hypothesized that mCAT might be beneficial only when ROS approaches pathological levels in older age and might not be advantageous at a younger age when basal ROS is low. We analyzed abundance and turnover of the global proteome in hearts and livers of young (4 month) and old (20 month) mCAT and wild-type (WT) mice. In old hearts and livers of WT mice, protein half-lives were reduced compared to young, while in mCAT mice the reverse was observed; the longest half-lives were seen in old mCAT mice and the sho...

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2015

Ageing Research Reviews, 2015

Aging cell, Aug 8, 2016

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with agi... more Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with aging and a broad spectrum of pathologies. We have previously shown that transgenic expression of the antioxidant enzyme catalase targeted to the mitochondria (mCAT) in mice reduces ROS, attenuates age-related disease, and increases lifespan. However, it has been increasingly recognized that ROS also has beneficial roles in signaling, hormesis, stress response, and immunity. We therefore hypothesized that mCAT might be beneficial only when ROS approaches pathological levels in older age and might not be advantageous at a younger age when basal ROS is low. We analyzed abundance and turnover of the global proteome in hearts and livers of young (4 month) and old (20 month) mCAT and wild-type (WT) mice. In old hearts and livers of WT mice, protein half-lives were reduced compared to young, while in mCAT mice the reverse was observed; the longest half-lives were seen in old mCAT mice and the sho...

Cancer has been at the forefront of scientific research in the last century. Numerous studies hav... more Cancer has been at the forefront of scientific research in the last century. Numerous studies have uncovered many faulty genes in cancer cells as well as afflicted molecular pathways that support the cancer phenotype. Protein kinase pathways have been widely implicated in variant cancers and have been shown to apply multiple mutant isoforms even within a single cancer as will be discussed below. Through molecular application of Darwinian genetics, vitality of specific pathways has emerged. Cancer cells deviate from physiologic proliferation and possess derived hallmarks that enable autonomous and unrestricted proliferation

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2015

Cardiovascular diseases are the leading cause of death in most developed nations. While it has re... more Cardiovascular diseases are the leading cause of death in most developed nations. While it has received the least public attention, aging is the dominant risk factor for developing cardiovascular diseases, as the prevalence of cardiovascular diseases increases dramatically with increasing age. Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. Mitochondria play a great role in these processes, as cardiac function is an energetically demanding process. In this review, we examine mitochondrial dysfunction in cardiac aging. Recent research has demonstrated that mitochondrial dysfunction can disrupt morphology, signaling pathways, and protein interactions; conversely, mitochondrial homeostasis is maintained by mechanisms that include fission/fusion, autophagy, and unfolded protein responses. Finally, we describe some of the recent findings in mitochondrial targeted treatments to help meet the challenges of mitochondrial dysfunction in aging.

Ageing Research Reviews, 2015

Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellu... more Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately associated with quality control mechanisms. This review provides a general overview of the clinical and cellular changes which manifest in cardiac aging, and the quality control mechanisms involved in maintaining homeostasis and retarding aging. These mechanisms include autophagy, ubiquitin-mediated turnover, apoptosis, mitochondrial quality control and cardiac matrix homeostasis. Finally, we discuss aging interventions that have been observed to impact cardiac health outcomes. These include caloric restriction, rapamycin, resveratrol, GDF11, mitochondrial antioxidants and cardiolipin-targeted therapeutics. A greater understanding of the quality control mechanisms that promote cardiac homeostasis will help to understand the benefits of these interventions, and hopefully lead to further improved therapeutic modalities.

Ageing Research Reviews, Sep 1, 2015

Aging cell, Aug 8, 2016

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with agi... more Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with aging and a broad spectrum of pathologies. We have previously shown that transgenic expression of the antioxidant enzyme catalase targeted to the mitochondria (mCAT) in mice reduces ROS, attenuates age-related disease, and increases lifespan. However, it has been increasingly recognized that ROS also has beneficial roles in signaling, hormesis, stress response, and immunity. We therefore hypothesized that mCAT might be beneficial only when ROS approaches pathological levels in older age and might not be advantageous at a younger age when basal ROS is low. We analyzed abundance and turnover of the global proteome in hearts and livers of young (4 month) and old (20 month) mCAT and wild-type (WT) mice. In old hearts and livers of WT mice, protein half-lives were reduced compared to young, while in mCAT mice the reverse was observed; the longest half-lives were seen in old mCAT mice and the sho...

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2015

Ageing Research Reviews, 2015

Aging cell, Aug 8, 2016

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with agi... more Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules associated with aging and a broad spectrum of pathologies. We have previously shown that transgenic expression of the antioxidant enzyme catalase targeted to the mitochondria (mCAT) in mice reduces ROS, attenuates age-related disease, and increases lifespan. However, it has been increasingly recognized that ROS also has beneficial roles in signaling, hormesis, stress response, and immunity. We therefore hypothesized that mCAT might be beneficial only when ROS approaches pathological levels in older age and might not be advantageous at a younger age when basal ROS is low. We analyzed abundance and turnover of the global proteome in hearts and livers of young (4 month) and old (20 month) mCAT and wild-type (WT) mice. In old hearts and livers of WT mice, protein half-lives were reduced compared to young, while in mCAT mice the reverse was observed; the longest half-lives were seen in old mCAT mice and the sho...

Cancer has been at the forefront of scientific research in the last century. Numerous studies hav... more Cancer has been at the forefront of scientific research in the last century. Numerous studies have uncovered many faulty genes in cancer cells as well as afflicted molecular pathways that support the cancer phenotype. Protein kinase pathways have been widely implicated in variant cancers and have been shown to apply multiple mutant isoforms even within a single cancer as will be discussed below. Through molecular application of Darwinian genetics, vitality of specific pathways has emerged. Cancer cells deviate from physiologic proliferation and possess derived hallmarks that enable autonomous and unrestricted proliferation

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2015

Cardiovascular diseases are the leading cause of death in most developed nations. While it has re... more Cardiovascular diseases are the leading cause of death in most developed nations. While it has received the least public attention, aging is the dominant risk factor for developing cardiovascular diseases, as the prevalence of cardiovascular diseases increases dramatically with increasing age. Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. Mitochondria play a great role in these processes, as cardiac function is an energetically demanding process. In this review, we examine mitochondrial dysfunction in cardiac aging. Recent research has demonstrated that mitochondrial dysfunction can disrupt morphology, signaling pathways, and protein interactions; conversely, mitochondrial homeostasis is maintained by mechanisms that include fission/fusion, autophagy, and unfolded protein responses. Finally, we describe some of the recent findings in mitochondrial targeted treatments to help meet the challenges of mitochondrial dysfunction in aging.

Ageing Research Reviews, 2015

Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellu... more Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately associated with quality control mechanisms. This review provides a general overview of the clinical and cellular changes which manifest in cardiac aging, and the quality control mechanisms involved in maintaining homeostasis and retarding aging. These mechanisms include autophagy, ubiquitin-mediated turnover, apoptosis, mitochondrial quality control and cardiac matrix homeostasis. Finally, we discuss aging interventions that have been observed to impact cardiac health outcomes. These include caloric restriction, rapamycin, resveratrol, GDF11, mitochondrial antioxidants and cardiolipin-targeted therapeutics. A greater understanding of the quality control mechanisms that promote cardiac homeostasis will help to understand the benefits of these interventions, and hopefully lead to further improved therapeutic modalities.