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BUFFALO, NY- January 2, 2025 – A new priority #research paper, featured as the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 22, was #published on December 29, 2024. The paper is titled “Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution.”

Researchers from the Chinese Academy of Sciences and Monash University developed a new way to measure biological aging in individual cell types. This new tool offers a more detailed understanding of how cells age, providing insights into diseases such as Alzheimer’s and liver pathologies, leading the way for more precise health assessments and targeted therapies.

Biological age refers to how old a person’s body is biologically, which may differ from their actual age in years. Typically, biological age is estimated using “epigenetic clocks,” which rely on DNA methylation patterns—chemical marks linked to aging. Standard methods analyze all the cells from a specific tissue at once, making it difficult to understand the aging processes in the different cell types that constitute the tissue.

To address this, researchers Huige Tong, Xiaolong Guo, Macsue Jacques, Qi Luo, Nir Eynon,m and Andrew E Teschendorff analyzed DNA samples from human brain and liver tissues to create a new analysis tool. With the help of advanced computer models, they studied changes in DNA methylation in samples from healthy and diseased individuals. By isolating biological aging within specific cell types, the team could better understand how these changes contribute to diseases like Alzheimer’s or liver conditions. 

The study revealed that certain brain cells, like neurons and glia, age faster in people with Alzheimer’s disease, suggesting that the aging of specific cell types plays a critical role in neurodegeneration. In liver diseases, such as fatty liver disease and obesity, the clock for liver cells showed signs of accelerated aging, making it a better tool than previous methods for detecting liver problems.

"We find that neuron and glia specific clocks display biological age acceleration in Alzheimer’s Disease with the effect being strongest for glia in the temporal lobe.” 

This new approach distinguishes the aging process within individual cell types from changes in the overall composition of cells in a tissue, offering a clearer view of how aging affects each specific cell type. This is crucial for identifying which cells are most affected by aging in certain diseases, guiding the development of targeted therapies. 

In conclusion, this study highlights the critical importance of precision in aging research, allowing deeper insights into the aging process and significant advancements in the prevention, diagnosis, and treatment of age-related diseases.

DOI - https://doi.org/10.18632/aging.206184

Corresponding author - Andrew E. Teschendorff - andrew@sinh.ac.cn

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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.

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)

Epigenetic Clocks Reveal Biological Age at Cell-Type Resolution

BUFFALO, NY- January 7, 2025 – A new #research perspective was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 22 on December 9, 2024, entitled “Nuclear lipid droplets: a novel regulator of nuclear homeostasis and ageing.”

In this article, Dr. Konstantinos Palikaras from the National and Kapodistrian University of Athens and Dr. Nektarios Tavernarakis from the University of Crete explore how tiny fat droplets, known as nuclear lipid droplets (nLDs), accumulate in the nucleus of cells as we age. Unlike regular lipid droplets, which store energy in the cytoplasm, these nuclear droplets may weaken the nucleus by disrupting critical cellular processes.

The authors suggest that excessive buildup of nLDs could lead to nuclear instability and may be linked to metabolic conditions such as fatty liver disease, obesity-related disorders, and premature aging. This highlights the potential role of nLDs in cellular aging and age-related diseases.

Previous research by the authors using Caenorhabditis elegans (C. elegans), a model organism commonly used to study aging, revealed the role of ATGL-1, an enzyme that regulates fat storage in the nucleus. When functioning properly, ATGL-1 helps maintain a healthy lipid balance. However, when it becomes inactive or overwhelmed, fat droplets build up around the nuclear lamina, making it more difficult for the cell to function properly.

“These findings establish excessive nuclear lipid deposition as a key hallmark of aging, with profound implications for nuclear processes such as chromatin organization, DNA repair, and gene regulation.”

The authors emphasize that lifestyle interventions, such as caloric restriction and better insulin regulation, can significantly reduce harmful nLD buildup, reinforcing the role of healthy metabolism in slowing cellular aging. They also call for further studies to understand how nLDs behave in human experimental models, particularly in patients with conditions like metabolic syndrome and progeria. A deeper understanding of these processes could lead to treatments designed to preserve cell health and delay age-related diseases.

In summary, by presenting nuclear lipid droplets as potential therapeutic targets, this research perspective presents a new path for exploring treatments aimed at combating age-related diseases driven by lipid dysregulation.

DOI - https://doi.org/10.18632/aging.206175

Corresponding authors - Konstantinos Palikaras - palikarask@med.uoa.gr, and Nektarios Tavernarakis - tavernarakis@imbb.forth.gr

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Keywords - aging, ATGL-1, HLH-30/TFEB, lipid droplet, non-linear optical phenomena, nucleus

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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Nuclear Lipid Droplets: Key Regulators of Aging and Nuclear Homeostasis

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BUFFALO, NY- January 8, 2025 – A new #research perspective was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 22 on December 18, 2024, entitled “Brown adipose tissue enhances exercise performance and healthful longevity.”

Researchers from Rutgers New Jersey Medical School, Dorothy E. Vatner, Jie Zhang, and Stephen F. Vatner, evaluated the role of brown adipose tissue (BAT), a special type of fat that burns calories to generate heat, in improving exercise endurance and supporting healthy aging. Unlike regular white fat, which stores energy, brown fat helps the body stay warm and boosts metabolism. According to the authors, this process may also help protect against health conditions such as obesity, diabetes, and cardiovascular disease.

This research perspective highlights key findings from multiple studies on BAT. While most studies have shown that exercise regulates BAT activation and increases BAT density, relatively few have demonstrated that BAT itself can directly increase exercise performance. 

One notable example involves RGS14 knockout mice, a genetically modified group known for their longer lifespan. When BAT from these mice was transplanted into regular mice, the recipients displayed improved running endurance just three days after the transplant. In contrast, brown fat from non-modified mice took much longer to produce similar improvements.

These findings highlight the unique properties of BAT in enhancing physical performance. The researchers emphasized also that BAT improves blood circulation and reduces cellular stress, which may help combat age-related muscle loss, fatigue, and metabolic decline.

The authors suggest that treatments designed to mimic the benefits of brown fat could lead to innovative approaches for improving energy levels, maintaining a healthy weight, and supporting heart health.

“​​In view of the ability of BAT to mediate healthful longevity and enhance exercise performance, it is likely that a pharmaceutical analog of BAT will become a novel therapeutic modality.”

In conclusion, continued research on this topic may lead to the development of promising new therapies that help older adults live more active lives while reducing the risk of chronic age-related conditions.

DOI - https://doi.org/10.18632/aging.206179

Corresponding author - Stephen F. Vatner - vatnersf@njms.rutgers.edu

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Keywords - aging, brown adipose tissue, white adipose tissue, healthful longevity, exercise, regulator of G protein signaling 14

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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Brown Fat Boosts Exercise Performance and Promotes Healthy Longevity

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BUFFALO, NY- January 14, 2025 – 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 22 on November 26, 2024, entitled “When do the pathological signs become evident? Study of human mesenchymal stem cells in MDPL syndrome.”

Researchers from the University of Rome Tor Vergata, Fondazione Policlinico Tor Vergata, Roma Tre University, and Meyer Children’s Hospital IRCCS have identified early cellular changes associated with Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy (MDPL) syndrome, a rare genetic aging disorder caused by a mutation in the POLD1 gene. MDPL leads to fat loss, distinct facial features, and metabolic disturbances. This study aimed to better understand how MDPL progresses at the cellular level.

MDPL syndrome is extremely rare, with only a few documented cases worldwide, making it difficult to study. To investigate the disease, researchers Spitalieri Paola, Guerrieri Lara, Murdocca Michela, Di Cesare Silvia, Maccaroni Serena, Pecorari Rosalba, Nardone Anna Maria, Candi Eleonora, Colasuonno Fiorella, Gori Giulia, Traficante Giovanna, Novelli Giuseppe, and Sangiuolo Federica, converted skin cells from three female MDPL patients and two healthy donors into human induced pluripotent stem cells (hiPSCs). These hiPSCs were then transformed into mesenchymal stem cells (MSCs), cells that can form tissues like bone and fat, which are primarily affected in MDPL syndrome.

The study revealed that MSCs from MDPL patients exhibited signs of premature aging much earlier than expected. The cells had irregular shapes, grew at a slower rate, and showed higher levels of cellular stress.

“These cells differentiate with lower efficiency, proliferate more slowly and have abnormal mitochondrial activity with increased production of ROS. Furthermore, the telomeres show evident shortening.” 

All the findings suggest that aging-related changes may occur long before patients display visible symptoms of the disease. This highlights the need for early diagnosis and intervention, which could delay or even prevent the most debilitating effects of MDPL syndrome.

In summary, this study offers new perspectives on the initial cellular impacts of MDPL, opening the door for the creation of novel treatments. The findings highlight the potential for personalized therapies and emphasize the critical role of lab-created hiPSCs in advancing research on rare genetic diseases and age-related conditions.

DOI - https://doi.org/10.18632/aging.206159

Corresponding author - Sangiuolo Federica - sangiuolo@med.uniroma2.it

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Keywords - aging, MDPL syndrome, MSCs, hiPSCs, POLD1 gene

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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When Do Pathological Signs Appear? Human Mesenchymal Stem Cells in MDPL Syndrome

BUFFALO, NY- January 15, 2025 – A new priority #review was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) on January 12, 2025, entitled “Mikhail ‘Misha’ Blagosklonny’s enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin.”

This review, written by Dr. David A. Barzilai, from Geneva College of Longevity Science and Healthspan Coaching LLC, summarizes the outstanding scientific contributions of the late Dr. Mikhail "Misha" Blagosklonny, Founding Editor-in-Chief of Aging. Dr. Blagosklonny’s research changed how researchers and scientists think about aging by introducing a new theory and promoting the use of rapamycin, an mTOR inhibitor, to slow aging and extend healthy life. Published shortly after his passing, this review honors Dr. Blagosklonny’s work and highlights how it challenged the traditional belief that aging is caused mainly by accumulated damage in the body.

Instead of describing aging as an accumulation of cellular damage, Dr. Blagosklonny’s Hyperfunction Theory redefined it as an ongoing biological process that goes into "overdrive" and leads to age-related diseases such as cancer, cardiovascular problems, and memory loss.

He identified the mTOR pathway—an important growth signal in the body—as a key driver of this process. His research showed that by using rapamycin, which slows down mTOR activity, it is possible to reduce aging-related diseases and promote longer, healthier lives.

Research supports many of Dr. Blagosklonny’s predictions about rapamycin’s benefits. Studies show that it can improve immune responses in older adults, making vaccines more effective. Other studies suggest rapamycin may help protect the heart, reduce harmful brain inflammation, and prevent the buildup of proteins linked to Alzheimer’s disease. Dr. Blagosklonny also proposed that rapamycin could reduce cancer risk by preventing excessive growth signals that contribute to tumor development.

Believing in rapamycin’s potential as a “longevity drug," Dr. Blagosklonny advocated for its careful use with medical supervision and precise dosing. He called for further research and even envisioned “longevity clinics” where personalized anti-aging treatments could be provided. The review also highlights ongoing scientific efforts to refine rapamycin therapies and explore new options with fewer side effects.

In conclusion, Dr. Blagosklonny has inspired a global shift toward viewing aging as a condition that can be managed rather than an inevitable decline. His research has left a legacy in the fields of geroscience, aging, and cancer prevention.

“This contribution will undoubtedly be remembered in the coming decades and beyond as an innovative contribution to our theoretical grasp of the aging process and a foundation for exploring effective therapeutic approaches.”

DOI - https://doi.org/10.18632/aging.206189

Corresponding author - David A. Barzilai - david.longevity@gmail.com

Video short - https://www.youtube.com/watch?v=3iOcIqfQdyI

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About Aging-US

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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Dr. Mikhail Blagosklonny’s Legacy: Hyperfunction Theory & Rapamycin

BUFFALO, NY- January 16, 2025 – 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 22 on December 2, 2024, entitled “Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry.”

Scientists from Chiba University in Japan and other institutions have discovered that the drug pioglitazone, commonly used to treat diabetes, may help prevent painful skin ulcers in people with Werner syndrome. Werner syndrome is a rare genetic condition that causes people to age faster than normal, leading to early gray hair, cataracts, and other age-related health problems. One of the most serious complications is skin ulcers, which affect nearly 70% of people with the disorder and can lead to severe pain, infections, and even amputations.

The study, led by first author Kazuto Aono and corresponding author Masaya Koshizaka, looked at 51 patients with Werner syndrome from the Japanese Werner Syndrome Registry. Over half of the patients had skin ulcers, and those with ulcers were generally older and had higher blood pressure. The research team found that patients who took pioglitazone were much less likely to have ulcers, even after accounting for age.

The research suggests that pioglitazone's ability to reduce inflammation helps wounds heal faster and prevents ulcers from forming. However, since the drug can cause side effects, like weaker bones, scientists recommend further studies to explore safer options, such as creams or gels made from pioglitazone that can be applied directly to the skin.

“Nanostructured hybrid materials loaded with pioglitazone are also being developed for clinical use and may be useful as wound dressings for ulcer treatment.” 

Although the study shows promising results, the authors emphasize that more long-term studies are needed to confirm how effective the treatment is besides the exploration of other factors, like diet and exercise, that may also help reduce the ulcers.

In conclusion, this study presents pioglitazone as a potential option to prevent skin ulcers in Werner syndrome patients. While further studies are needed, these findings provide hope for better treatments.

DOI - https://doi.org/10.18632/aging.206161

Corresponding author - Masaya Koshizaka - overslope@chiba-u.jp

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Keywords - aging, Werner syndrome, skin ulcer, metformin, pioglitazon, progeroid syndrome

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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Fewer Skin Ulcers in Werner Syndrome Patients Treated with Pioglitazone

Get ready for 4 more years of laughs as Michael Knowles looks back at Donald Trump’s funniest moments! From his epic trolling of the press to hilarious nicknames and unforgettable interactions with world leaders, we’re reliving the best of 45 as we count down to 47. Don’t miss this trip down memory lane—and get ready for what’s next!

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Trump’s Funniest Highlights from 45—And Now, 4 More Years!

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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

Bask in the simple joys of being right. The Michael Knowles Show cuts through the madness of our politics and culture, analyzing the top stories of the day. Monday through Friday.

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