(Press-News.org) Aging-US Issue 1 Volume 13 features "PAM (PIK3/AKT/mTOR) signaling in glia: potential contributions to brain tumors in aging" which reported that despite a growing proportion of aged individuals at risk for developing cancer in the brain, the prognosis for these conditions remains abnormally poor due to limited knowledge of underlying mechanisms and minimal treatment options.
While cancer metabolism in other organs is commonly associated with upregulated glycolysis and hyperactivation of PIK3/AKT/mTOR pathways, the unique bioenergetic demands of the central nervous system may interact with these oncogenic processes to promote tumor progression in aging. Specifically, constitutive glycolysis and PIK3/AKT/mTOR signaling in glia may be dysregulated by age-dependent alterations in neurometabolic demands, ultimately contributing to pathological processes otherwise associated with PIK3/AKT/mTOR induction.
Although several limitations to this theoretical model exist, the consideration of aberrant PIK3/AKT/mTOR signaling in glia during aging elucidates several therapeutic opportunities for brain tumors, including non-pharmacological interventions.
Dr. Kamel Khalili from Temple University said, "Cancer in the brain is significantly less common than in other organs, but disproportionately contributes to higher rates of mortality"
Since metabolic syndrome is an independent risk factor for worse prognosis in patients with certain CNS tumors, bioenergetic processes in particular are emerging as important variables in tumor neuropathology.
Among primary cell types implicated in tumor pathogenesis, minimal contributions are observed from non-glia; less than 10% of all tumors manifest as lymphomas, meningiomas, embryonal tumors, or choroid plexus carcinomas, among others.
As tumors of glial origin account for the vast majority of all CNS cancers, age-dependent variation in glial functioning may particularly contribute to tumor pathology in the brain.
Within the CNS, astrocytes in particular have long been associated with metabolic homeostasis and are the most common cell type associated with tumor pathology.
Given that glia are responsible for maintaining energy homeostasis of the CNS by utilizing similar metabolic pathways of cancer cells, chronic alterations in bioenergetic demands during aging.
The Khalili Research Team concluded in their Aging-US Review Article that in particular, the inhibition of PI3K's downstream effectors, AKT and mTOR, may prove to reliably mitigate proliferation, motility and viability in glioma cells.
Additionally, PI3K inhibitors are emerging as potent antagonistic agents in various types of cancer, including gliomas.
While cancer cells have been shown to overcome this inhibition, evidence from preclinical models suggest the combination of dietary manipulations as well as PI3K inhibitors can augment the inhibition of PAM signaling and increase therapeutic efficacy.
Compared to mice treated with PI3K inhibitors alone, mice maintained on a ketogenic diet during treatment display significantly decreased mortality rates following intracranial implantation of aggressive human gliomas.
Although further validation of these targets is required, the modulation of PAM signaling to mitigate glioma progression in the aging CNS may prove efficacious and merits consideration.
INFORMATION:
Full Text - https://www.aging-us.com/article/202459/text
Correspondence to: Kamel Khalili email: kamel.khalili@temple.edu
Keywords: glioma, aging, bioenergetics
About Aging-US
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.
To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl
Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact
18009220957x105
MEDIA@IMPACTJOURNALS.COM
Aging-US published "Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment" which reported that here, the authors investigated nicotinamide mononucleotide, a precursor of nicotinamide adenine dinucleotide, in a retinal detachment induced photoreceptor degeneration.
NMN administration after RD resulted in a significant reduction of TUNEL photoreceptors, CD11b macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content, and a preservation of the outer nuclear layer thickness.
NMN administration significantly increased NAD levels, SIRT1 protein expression, and heme oxygenase-1 expression.
Delayed NMN administration still exerted protective effects after RD.
This ...
A nuclear war could trigger an unprecedented El Niño-like warming episode in the equatorial Pacific Ocean, slashing algal populations by 40 percent and likely lowering the fish catch, according to a Rutgers-led study.
The research, published in the journal END ...
DALLAS, Jan. 25, 2021 -- Psychological health can positively or negatively impact a person's health and risk factors for heart disease and stroke, according to "Psychological Health, Well-Being, and the Mind-Heart-Body Connection," a new American Heart Association Scientific Statement, published today in the Association's flagship journal Circulation. The statement evaluates the relationship between psychological health and heart health, summarizing ways to help improve psychological health for people with and at risk for heart disease.
"A person's mind, heart and body are all interconnected and interdependent in what can be termed 'the mind-heart-body-connection,'" said Glenn N. Levine, M.D., FAHA, master clinician and professor of medicine at ...
DALLAS, Jan. 25, 2021 -- The continued global burden of stroke and how it disproportionately affects women are highlighted in new science published online today in the February issue of Stroke, a journal of the American Stroke Association, a division of the American Heart Association. Stroke editors selected nine manuscripts focused on stroke disparities in women in this collaboration with Go Red for Women®, the Association's global movement to end heart disease and stroke in women.
"Stroke continues to be a leading cause of death and disability worldwide, with women being more adversely affected by the global burden of stroke," said Stroke Editor-In-Chief Ralph L. Sacco, M.D., M.S., FAHA, ...
Scientists have identified a key nutrient source used by algae living on melting ice surfaces linked to rising sea levels.
The Greenland ice sheet - the second largest ice body in the world after the Antarctic ice sheet - covers almost 80% of the surface of Greenland. Over the last 25 years, surface melting and water runoff from the ice sheet has increased by about 40%.
The international research team, led by the University of Leeds, analysed samples from the southwestern margin on Greenland's 1.7 million km² ice sheet over two years.
They discovered that phosphorus containing minerals may be driving ever-larger algal blooms on the Greenland Ice Sheet. As the algal blooms grow they darken the ice surface, decreasing albedo - ...
EAST LANSING, Mich. - An international team of researchers led by Michigan State University's Morteza Mahmoudi has developed a new method to better understand how nanomedicines -- emerging diagnostics and therapies that are very small yet very intricate -- interact with patients' biomolecules.
Medicines based on nanoscopic particles have the promise to be more effective than current therapies while reducing side effects. But subtle complexities have confined most of these particles to research labs and out of clinical use, said Mahmoudi, an assistant professor in the Department of Radiology and the Precision Health Program.
"There's been a considerable investment of taxpayer money in cancer nanomedicine research, but that research hasn't successfully translated ...
Even before public announcements of the first cases of COVID-19 in Europe were made, at the end of January 2020, signals that something strange was happening were already circulating on social media. A new study of researchers at IMT School for Advanced Studies Lucca, published in END ...
The rate at which ice is disappearing across the planet is speeding up, according to new research.
And the findings also reveal that the Earth lost 28 trillion tonnes of ice between 1994 and 2017 - equivalent to a sheet of ice 100 metres thick covering the whole of the UK.
The figures have been published today (Monday, 25 January) by a research team which is the first to carry out a survey of global ice loss using satellite data.
The team, led by the University of Leeds, found that the rate of ice loss from the Earth has increased markedly within the past three decades, from 0.8 trillion tons per year in the 1990s to 1.3 trillion tons per year by 2017.
Ice melt across the globe ...
Female childhood cancer survivors face a lower likelihood of becoming pregnant than women in the general population, but once pregnant, they are not more likely to undergo an abortion. The findings come from a new study published early online in CANCER, a peer-reviewed journal of the American Cancer Society.
Cancer survivors might be reluctant to start a family due to concerns for their children's health as well as the potential recurrence of their own cancer. This could lead to a greater likelihood of induced abortions in female survivors who become pregnant.
To examine whether pregnancies of childhood cancer survivors are more likely to end with ...
AUGUSTA, Ga. (January 25, 2021) - Immediately after a traumatic brain injury and as long as one year later, there are increased levels of immune cells called ILCs in the brain promoting inflammation, which can worsen brain damage, scientists report.
They also report for the first time that the cell energy sensor AMPK is a brake that can stop what becomes a chronic state of destructive inflammation driven by these ILCs, or innate lymphoid cells.
"We think ILCs are kind of a master regulator of all that inflammation happening within the brain," says Dr. Krishnan Dhandapani, neuroscientist in the Department of Neurosurgery at the Medical College of Georgia at Augusta University. "It's like the ...
