BUFFALO, NY- August 14, 2024 – A new #editorial was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 14 on July 17, 2024, entitled, “Recalibrate concepts of epigenetic aging clocks in human health.”

As detailed in the opening of this editorial, DNA methylation-based epigenetic clocks are used as biomarkers of biological age in human health. Multiple epigenetic clocks have rapidly emerged in the past decade by modeling DNA methylation changes with age in large cohorts, primarily using peripheral blood samples. Despite efforts to understand the functional implications of features used to estimate biological age, the underlying mechanisms of these clocks remain poorly understood, leading to potential misinterpretations of their associations with health outcomes.

Researchers Ze Zhang, Brock C. Christensen, and Lucas A. Salas from the Divisions of Population Sciences and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, the Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Dartmouth Cancer Center, Dartmouth-Hitchcock Medical Center, and the Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College explored the association of 12 immune cell types with epigenetic age acceleration (EAA) in both healthy and diseased populations. 

Their work sheds light on the complex interplay between immune cell composition and epigenetic aging, utilizing high-resolution methylation cytometry in blood samples.

“In this editorial, we aim to address the key implications of our study on epigenetic aging clocks in human health from a broader perspective. While epigenetic clocks are widely hyped as aging biomarkers today, it's essential to recalibrate some fundamental concepts in this field.”

DOI - https://doi.org/10.18632/aging.206027

Corresponding author - Lucas A. Salas - lucas.a.salas@dartmouth.edu

Video short - https://www.youtube.com/watch?v=9lV-pkYm22M

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Keywords - aging, epigenetics, DNA methylation, epigenetic clock, epigenetic age acceleration, methylation cytometry

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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Aging (Aging-US)

Recalibrating Principles of Epigenetic Aging Clocks in Human Health

BUFFALO, NY- December 2, 2024 – A new #review was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 21, titled, “Sleep deprivation in dementia comorbidities: focus on cardiovascular disease, diabetes, anxiety/depression and thyroid disorders.”


The review, authored by Upasana Mukherjee, Ujala Sehar, Malcolm Brownell, and P. Hemachandra Reddy from Texas Tech University Health Sciences Center, compiles findings from recent studies on how sleep problems—such as insomnia, sleep apnea, and disrupted sleep cycles—can worsen dementia and accelerate cognitive decline. It also emphasizes the profound impact of these sleep disorders on caregivers, who often face burnout and emotional stress. 

Dementia is a condition that significantly impairs the ability to think, remember, and make decisions, making everyday life increasingly difficult to manage. Sleep problems are a major challenge for individuals with dementia, with more than half experiencing disturbed sleep. These disturbances include difficulty falling asleep, staying asleep, or engaging in nighttime wandering.

Such issues go beyond causing fatigue—they accelerate memory loss, increase confusion, and raise the risk of behavioral symptoms like agitation. Addressing sleep challenges is critical to improving quality of life for both patients and their caregivers. Caregivers, who often support loved ones around the clock, face significant stress when dealing with these sleep disorders.

“This situation creates a vicious cycle where caregiver distress exacerbates patient symptoms, further increasing the burden on caregivers.”
This review also explores how other illnesses, common in older adults with dementia, worsen sleep disturbances. Conditions such as diabetes, thyroid dysfunction, heart disease, and anxiety disrupt sleep, and poor sleep then worsens both the dementia and the underlying illnesses. For instance, untreated sleep apnea can significantly accelerate cognitive decline in people with dementia.

To improve sleep for dementia patients, the authors recommend holistic approaches that address both sleep disturbances and related health conditions. Simple changes, such as establishing a regular bedtime routine, reducing nighttime noise, and encouraging daytime physical activity, can significantly enhance sleep quality.

Non-pharmacological treatments, including light therapy and cognitive behavioral therapy for insomnia, have also shown promise. Managing coexisting conditions such as diabetes or anxiety can help reduce the severity of sleep issues. The authors emphasize the need for more research into targeted, multidisciplinary approaches to effectively manage sleep disturbances, improve patient well-being, and reduce caregiver stress.

In conclusion, this review highlights the critical need for a more comprehensive approach to dementia care. Improving sleep could slow the progression of dementia, reduce caregiver stress, and enhance the quality of life for everyone involved. As dementia cases rise worldwide, addressing sleep issues will become an increasingly important aspect of care.

DOI - https://doi.org/10.18632/aging.206157

Corresponding author - P. Hemachandra Reddy - hemachandra.reddy@ttuhsc.edu

Video short - https://www.youtube.com/watch?v=lrrrXabMjjM

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The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

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Sleep Deprivation in Dementia: Heart Disease, Diabetes, Anxiety, and Thyroid Disorders

BUFFALO, NY - December 3, 2024 – A new #review was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists." 

Authored by Theia Minev, Shani Balbuena, Jaya Mini Gill, Francesco M. Marincola, Santosh Kesari, and Feng Lin from CureScience Institute, Sonata Therapeutics, and Pacific Neuroscience Institute and Providence Saint John’s Health Center, this review explores the potential role of mesenchymal stem cells (MSCs) in cancer treatment. These stem cells can naturally target tumors and deliver therapeutic agents directly to cancer cells, potentially improving treatment outcomes while reducing side effects commonly associated with traditional therapies like chemotherapy. However, the authors also note significant challenges, pointing out that under certain conditions, MSCs may unintentionally promote tumor growth, highlighting the need for careful therapeutic design.

MSCs are cells that can develop in different types of tissues, such as bone, fat, or cartilage, and act as natural repair agents. What makes them particularly special is their ability to respond to biological signals, like inflammation, which is often present in cancer. This enables them to locate tumors, and once there, they can deliver cancer treatments directly to the affected area.

Clinical trials are already investigating MSC-based treatments for cancers such as brain tumors, melanoma, and ovarian cancer. Some results are promising, showing that MSCs can effectively deliver treatments and boost the immune system’s fight against cancer. However, other trials have also revealed the complexities of MSC behavior, including variability in their effects and the potential to create conditions that support tumor growth. 

“This variability may be due to the tumor immune microenvironment’s effects, where immune cells are inhibited by various factors, creating a conducive environment for tumor growth.” 

The authors also suggest that “Developing personalized MSC therapies tailored to the specific characteristics of a patient’s tumor and immune system could enhance the efficacy and safety of MSC-based treatments.” Achieving this requires a deeper understanding of how MSCs interact with cancer cells and their surrounding environment.

In conclusion, this review highlights both the potential and challenges of (MSCs in cancer therapy. With ongoing research and technological advancements, MSCs could become a key component of personalized cancer treatments, offering new hope for patients worldwide.

DOI - https://doi.org/10.18632/oncotarget.28672

Correspondence to - Feng Lin - flin@curescience.org

Video short - https://www.youtube.com/watch?v=Wwc3zDDitlc

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About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Oncotarget

Mesenchymal Stem Cells in Cancer Immunotherapy: Promises and Challenges

In the this episode of the Longevity & Aging Series, Dr. Meesha Dogan, CEO of Cardio Diagnostics, joined host Dr. Evgeniy Galimov to discuss her pioneering work in #artificialintelligence, #epigenetics, and #genetics in developing next-generation DNA-based tests for preventing and managing #cardiovasculardisease globally.

Video interview - https://www.youtube.com/watch?v=9yPzl10vDlQ

Video transcription - https://www.aging-us.com/interviews/longevity-aging-series-s2-e4-dr-meesha-dogan

Cardio Diagnostics - https://cdio.ai/

About Evgeniy Galimov

Evgeniy Galimov, Ph.D., is a researcher and data scientist with experience in research in ageing and age-related diseases. He studied bioengineering and bioinformatics and received PhD from Lomonosov Moscow State University. Evgeniy’s early research was devoted to molecular mechanisms of cancer, atherosclerosis and neurodegeneration, later he switched to modelling the evolution of ageing and published several papers about it. Evgeniy also has start-up experience and applied machine learning to predict lifespan in model organisms and coronary heart disease in patients based on blood biomarkers. Additionally, Dr. Galimov developed a deep-learning model capable of classifying lifespan in C. elegans and identifying morphological features that influence the prediction. 

Currently, Dr. Galimov is engaged in Real World Evidence health data research focused on age-related pathologies.

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Please visit our website at https://www.Aging-US.com​​ and connect with us:

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Longevity & Aging Series (S2, E4): Dr. Meesha Dogan

BUFFALO, NY - December 4, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on November 22, 2024, entitled “B7-H4: A potential therapeutic target in adenoid cystic carcinoma." 

Researchers Luana Guimaraes de Sousa and Renata Ferrarotto from The University of Texas MD Anderson Cancer Center made an important discovery about adenoid cystic carcinoma (ACC), a rare and aggressive cancer of the secretory glands. The study found that B7-H4, an inhibitory immune checkpoint, helps ACC tumors avoid attacks from the immune system. This discovery could lead to new treatments for ACC, which currently has very limited options for patients, especially when the cancer spreads to other organs.

ACC is known for behaving in two distinct ways. The aggressive form, called ACC-I, spreads quickly to organs like the liver and lungs and leads to a short survival time of approximately three years. The less aggressive form, ACC-II, grows more slowly and often allows patients to live much longer, sometimes over 20 years. However, treatment options for both forms are limited, and once the cancer spreads, it becomes difficult to treat.

The study showed that the protein B7-H4 is found at high levels in the aggressive ACC-I tumors. This protein blocks immune cells from entering the tumor, allowing the cancer to grow without being attacked by the immune system. Patients with high levels of B7-H4 in their tumors were found to have worse survival outcomes.

To explore possible treatments, the researchers tested a new drug called AZD8205, designed to specifically target and block B7-H4. In preclinical tests on mice, the drug showed remarkable success. Tumors derived from patients shrank in every case, and in many cases of aggressive ACC, the tumors disappeared completely. Importantly, the drug had little effect on less aggressive ACC-II tumors, which have lower levels of B7-H4. This shows that the treatment is highly specific to tumors with high B7-H4 levels. 

These results have already led to clinical trials that are testing similar drugs in patients with ACC. 

“These trials represent attractive, rationale therapeutic opportunities for patients facing this rare, aggressive, and chemo-refractory disease, for which no systemic therapy is currently available.”

In conclusion, this discovery represents a significant breakthrough in ACC research, identifying B7-H4 as a crucial factor in cancer growth and immune evasion. By leading the way for personalized treatments, it offers promising new therapeutic options and the potential for improved outcomes for ACC patients.

DOI - https://doi.org/10.18632/oncotarget.28661

Correspondence to - Renata Ferrarotto - rferrarotto@mdanderson.org

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About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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B7-H4 as a Therapeutic Target in Adenoid Cystic Carcinoma

BUFFALO, NY- December 4, 2024 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 21 on November 22, 2024, entitled, “The effects of young and aged, male and female megakaryocyte conditioned media on angiogenic properties of endothelial cells.”

Researchers Murad K. Nazzal, Hanisha L. Battina, Nikhil P. Tewari, Sarah L. Mostardo, Rohit U. Nagaraj, Donghui Zhou, Olatundun D. Awosanya, Saveda K. Majety, Sue Samson, Rachel J. Blosser, Ushashi C. Dadwal, Patrick L. Mulcrone, and Melissa A. Kacenaat from Indiana University School of Medicine and Richard L. Roudebush Veterans' Administration Medical Center, have uncovered how certain bone marrow cells, called megakaryocytes (MKs), promote the growth of new blood vessels (angiogenesis) to aid in bone healing. Their findings help explain why healing slows with age and offer insights into potential treatments to accelerate fracture recovery in older adults.

Broken bones are common in older adults, and slower healing can lead to complications and longer hospital stays. Accelerating the healing process could significantly improve the quality of life for millions.

In this study, researchers investigated the effects of substances secreted by MKs, collected from young and older male and female mice. These substances, known as conditioned media (CM), were tested for their ability to stimulate the growth and function of endothelial cells (EC), which form the building blocks of blood vessels. Blood vessels play a critical role in healing by delivering oxygen and nutrients to damaged areas, making angiogenesis a vital part of the recovery process.

The results showed that CM from younger MKs mice was more effective at helping blood vessels grow. Interestingly, MKs from female mice performed better than those from males, regardless of age. For example, substances from female MKs mice boosted blood vessel growth by over 115% and significantly improved the movement of cells needed for healing. 

The researchers also studied changes in genes related to blood vessel growth, and found that aging affects how these genes work. These changes may explain why older people heal more slowly after breaking a bone. 

“An understanding of which factors regulate which mechanisms of EC functionality may allow for isolation of one or a few factors that influence EC migration changes with aging, resulting in the development of targeted therapy to improve EC migration, subsequent angiogenesis, and fracture healing.” 

In conclusion, this research paves the way for developing new therapies to help older individuals recover from fractures more quickly, reducing pain and improving mobility. One potential approach could involve creating treatments that replicate the effects of MKs from younger individuals or isolating the specific substances that promote blood vessel growth. This represents an important step toward addressing the growing challenge of delayed healing in an aging population.

DOI - https://doi.org/10.18632/aging.206077

Corresponding authors - Patrick L. Mulcrone - pamulcro@iu.edu, and Melissa A. Kacena - mkacena@iupui.edu

About Aging-US

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Please visit our website at https://www.Aging-US.com​​.

MEDIA@IMPACTJOURNALS.COM

Effects of Megakaryocyte Conditioned Media on Endothelial Cell Angiogenesis

“Precision medicine is an innovative approach to disease prevention and treatment that considers differences in people’s genes, injuries, environments, and lifestyles to target the right therapies to the right patients at the right time.”

Could a deeper understanding of one of the deadliest lung cancers lead to more effective treatments? Recent research offers a promising way forward, aiming to improve patient outcomes and provide clinicians with valuable insights.

Small Cell Lung Cancer (SCLC) is a particularly aggressive form of lung cancer. It spreads fast and does not always respond well to conventional therapies such as chemotherapy. Although SCLC accounts for around 15% of all lung cancer cases, survival rates are extremely low. Only less than 5% of patients live more than five years after diagnosis. These alarming statistics highlight the critical need for new treatments. A team of researchers from the Federal University of Ceará, working together with collaborators from Argentina and Spain, may have found part of the solution.

Full blog - https://www.oncotarget.org/2024/12/04/small-cell-lung-cancer-advancing-precision-medicine-with-biomarker-research/

Paper DOI - https://doi.org/10.18632/oncotarget.28660

Correspondence to - Fabio Tavora - fabio.tavora@argospatologia.com

Author interview - https://www.youtube.com/watch?v=bJO2MD8AXkY

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Keywords - cancer, DLL3, pathology, biomarkers, qupath, small cell carcinoma

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Small Cell Lung Cancer: Advancing Precision Medicine with Biomarker Research

Cancer and aging are two sides of age-related tumorigenesis.

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

Recalibrating Principles of Epigenetic Aging Clocks in Human Health

Aging (Aging-US) Podcast