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Call for Papers: Special Collection Honoring Dr. Mikhail (Misha) Blagosklonny

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Dr. Mikhail Blagosklonny
Dr. Mikhail Blagosklonny

“This special collection will explore key themes central to Dr. Blagosklonny’s scientific contributions, with a focus on mechanistic insights, translational approaches, and theoretical perspectives.”

BUFFALO, NY — April 3, 2025 — Aging (Aging-US) is pleased to announce a special Call for Papers for a commemorative collection honoring the legacy of Dr. Mikhail (Misha) Blagosklonny, the founding editor of the journal and a pioneer in aging biology. His groundbreaking work shaped fundamental concepts in the field, particularly regarding the role of mTOR in aging and cancer, the use of rapamycin, bypassing senescence during the process of transformation, personalized medicine, and theories on why we age.

This special collection will explore key themes central to Dr. Blagosklonny’s scientific contributions, with a focus on mechanistic insights, translational approaches, and theoretical perspectives. We invite original research, reviews, and perspective articles covering topics such as:

  • The role of mTOR in aging and age-related diseases
  • Rapamycin and other pharmacological strategies to extend lifespan
  • Senescence bypass and its implications for cancer and regenerative medicine
  • Personalized medicine approaches in aging and longevity research
  • Theoretical models and evolutionary perspectives on aging

The special issue will be guest-edited by leading scientist in the field, David Gems, who will oversee the selection of high-quality contributions that reflect the depth and impact of Dr. Blagosklonny’s work.

We encourage researchers working on these topics to submit their manuscripts and contribute to this tribute to one of the most influential figures in aging research.

SUBMISSION DETAILS:

We look forward to your contributions to this special issue and to honoring Dr. Blagosklonny’s enduring impact on the field of aging research.

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Senolytic Compounds Show Promise in Targeted Alzheimer’s Treatments

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“Cellular senescence is a hallmark of aging and the age-related condition, Alzheimer’s disease (AD).”

Could a class of drugs that clear aging cells also help treat Alzheimer’s disease? A recent study, featured as the cover for Aging (Volume 17, Issue 3), titled “Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer’s disease,” suggests they might—and with remarkable precision.

Understanding Alzheimer’s Disease

Alzheimer’s disease is a progressive neurological disorder that gradually steals memory, independence, and a person’s sense of identity. A defining feature of Alzheimer’s is the buildup of amyloid-β (Aβ) plaques—sticky protein clumps that interfere with communication between brain cells. This disruption is closely linked to changes in a group of enzymes called cholinesterases, especially acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes normally play a vital role in regulating neurotransmitters critical for memory, learning, and cognitive function. In Alzheimer’s, however, their behavior changes significantly, particularly when they interact with Aβ plaques.

The Study: Exploring Senolytics for Alzheimer’s Enzyme Inhibition

A research team from Dalhousie University in Canada looked into whether senolytic compounds—a class of drugs that eliminate damaged, aging cells often referred to as “zombie” cells—could also target the harmful forms of cholinesterase enzymes found in Alzheimer’s disease. Their goal was to see if these compounds could selectively inhibit the disease-associated versions of AChE and BChE, without affecting the healthy forms that are essential for normal brain function.

Led by Dr. Sultan Darvesh, the study tested six compounds: five senolytics—dasatinib, nintedanib, fisetin, quercetin, and GW2580—and one nootropic, meclofenoxate hydrochloride, known for its memory-enhancing potential. The researchers used post-mortem brain tissue from Alzheimer’s patients, enzyme activity assays, and computer modeling to examine how these compounds interact with the enzymes.

The Challenge: Targeting the Right Enzymes

One of the limitations of current Alzheimer’s treatments is that they do not distinguish between the normal and the altered forms of cholinesterases. While these drugs can raise levels of the memory-related chemical acetylcholine and improve cognitive function, they often come with side effects due to their broad activity. A more precise approach—targeting only the versions of AChE and BChE tied to Aβ plaques—could offer better outcomes with fewer drawbacks.

The Results: Senolytics Show Precision in Enzyme Targeting

The results were promising. Some of the senolytics tested, like dasatinib and nintedanib, effectively blocked the cholinesterases attached to Aβ plaques without affecting the normal versions of these enzymes in healthy brain tissue. Meclofenoxate also showed strong activity against the disease-associated forms. Interestingly, this selectivity was linked to how these compounds bind to the enzymes. Instead of locking onto the main active site, many of them attached to alternative regions, known as allosteric sites, which are only altered in the plaque-associated forms. This type of binding allowed the compounds to distinguish between harmful and healthy enzymes.

The Breakthrough: Targeting the Disease, Preserving the Brain

This study is the first to show that certain senolytic and cognitive-enhancing drugs can selectively inhibit the dysfunctional versions of cholinesterases found in Alzheimer’s without affecting their normal forms. This level of precision could mark a major step forward in Alzheimer’s therapy.

The Impact: A Dual-Action Path to Treating Alzheimer’s

By focusing on only the problematic forms of AChE and BChE, this approach could lead to Alzheimer’s treatments that better preserve cognitive function while avoiding side effects. The research also bridges two important areas of study: aging and neurodegeneration. It suggests that drugs developed to slow aging might also be used as targeted treatments for Alzheimer’s, offering a two-in-one therapeutic advantage. 

Future Perspectives and Conclusion

Although more research is needed, especially in living models and clinical trials, the potential of the findings is encouraging. They lead the way for a new generation of Alzheimer’s treatments that are more targeted and safer.

By understanding better how aging and brain disease intersect at the cellular level, scientists may be moving closer to developing more effective and personalized approaches to combat Alzheimer’s.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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How Environmental Chemicals May Accelerate Biological Aging

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“Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging.”

Could the air we breathe, the food we eat, or the chemicals in our everyday environment be accelerating our aging process? A recent study published in Aging suggests that exposure to certain environmental chemicals may be linked to faster biological aging through changes in DNA. These findings could have major implications for public health and longevity.

Understanding How Scientists Measure Aging at the DNA Level

Aging is not just about wrinkles and gray hair—it happens at the molecular level too. Scientists use epigenetic clocks to measure biological aging, which can differ from a person’s actual chronological age. These clocks track DNA methylation, a type of chemical modification that can change over time due to environmental factors like diet, pollution, and chemical exposure. Until now, there has been little research into how widespread environmental chemicals impact these aging markers. 

The Study: Investigating the Impact of Environmental Pollutants on Aging

A research team led by first author Dennis Khodasevich and corresponding author Andres Cardenas from Stanford University, conducted an exposome-wide association study to examine how different environmental pollutants affect epigenetic aging. Using data from the National Health and Nutrition Examination Survey (NHANES), they analyzed blood and urine samples from 2,346 adults aged 50 to 84. The study measured 64 environmental chemicals, including heavy metals, pesticides, plastics, and tobacco-related compounds, to identify potential links to accelerated aging. The study titled “Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey,” was published in Aging on February 11, 2025.

The Challenge: Unraveling the Complex Relationship Between Toxins and Aging

For years, scientists suspected that environmental toxins might contribute to aging, but most studies focused on a small set of chemicals. This work took a broader and more systematic approach to analyze a wide range of pollutants that people are commonly exposed to. The goal was to uncover previously unknown connections between chemical exposure and biological aging at the genetic level.

The Results: Environmental Chemicals That Speed Up Aging

The study identified several chemicals that were significantly associated with epigenetic age acceleration. One of the most concerning findings was the impact of cadmium, a toxic heavy metal found in cigarette smoke, industrial pollution, and some foods. Higher levels of cadmium in the blood were linked to faster aging across multiple epigenetic clocks.

Another key finding was the role of cotinine, a biomarker of tobacco exposure. People with higher levels of cotinine in their system showed signs of accelerated DNA aging, reinforcing the long-known link between smoking and premature aging.

The study also found that lead and dioxins, commonly found in industrial pollutants and certain processed foods, might contribute to biological aging. Interestingly, some pollutants, like certain polychlorinated biphenyls (PCBs), were associated with slower aging, though the health effects of these compounds remain unclear.

The Breakthrough: Why Cadmium and Smoking Are Major Aging Accelerators

This research highlights cadmium as a major environmental driver of aging. Since cadmium exposure comes from both smoking and diet, reducing it could be a key anti-aging strategy. The findings also provide further evidence that smoking is one of the most significant factors influencing epigenetic aging.

Reducing exposure to cigarette smoke, polluted air, and contaminated foods could help slow down DNA aging and potentially increase lifespan.

The Impact: How These Findings Can Influence Health Policies and Personal Choices

The results of this study could lead to stronger environmental regulations on heavy metals and toxic pollutants. Policymakers may push for stricter air quality standards, better food safety regulations, and more public health initiatives to reduce exposure to aging-accelerating chemicals.

For individuals, this research reinforces the importance of reducing exposure to toxins. Avoiding cigarette smoke, choosing organic and non-processed foods, and being mindful of products containing chemicals could help protect DNA health and promote longevity. 

Future Perspectives and Conclusion

While this study provides strong evidence that environmental toxins influence aging, further research is needed to determine whether reducing exposure can slow down or even reverse epigenetic aging. Future studies could focus on younger populations and examine how lifestyle changes interact with these environmental exposures.

For now, taking steps to avoid cigarette smoke, limit exposure to heavy metals, and maintain a clean diet could be practical ways to protect long-term health and slow down biological aging.

By understanding how environmental pollutants impact aging, individuals and policymakers can make informed decisions that promote a longer, healthier life.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Click here to subscribe to Aging publication updates.

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How Radiation Therapy Affects Tumors: Glioblastoma vs. Low-Grade Gliomas

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“These insights underscore the importance of personalized treatment approaches and the need for further research to improve radiotherapy outcomes in cancer patients.”

Radiation therapy or radiotherapy, is a common treatment for cancer, but its effectiveness differs across patients. A recent study published as the cover for Volume 17, Issue 2 of Aging explored why this happens. The findings provide valuable insights, particularly for brain cancers like glioblastoma (GBM) and low-grade gliomas (LGG).

Understanding Glioblastoma and Low-Grade Gliomas

Glioblastoma and LGG are both brain tumors, but they behave in very different ways. GBM is highly aggressive, with most patients surviving only 12 to 18 months, even with surgery, chemotherapy, and radiation therapy. LGG, on the other hand, grows more slowly, and many patients live for decades with proper care.

Despite their differences, LGG and GBM are biologically linked. Some LGG tumors eventually transform into GBM, making early treatment decisions critical. Given radiation therapy’s effectiveness in GBM, it has often been assumed that LGG patients would also benefit from it. However, a new study titled “Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas” challenges this assumption.

The Study: Investigating Radiation Therapy’s Impact on Cancer Patients Survival

A research team led by first author Alexander Veviorskiy from Insilico Medicine AI Limited, Abu Dhabi, UAE, and corresponding author Morten Scheibye-Knudsen from the Center for Healthy Aging, University of Copenhagen, studied how radiation therapy affects cancer patient survival. They examined data from The Cancer Genome Atlas (TCGA), which includes 32 types of cancer. When they found that GBM and LGG had very different survival outcomes after radiation, they decided to focus on these two types of brain cancer. To learn more about their differences, gene expression and molecular pathways connected to radiation therapy responses were studied.

The Challenge: Why Radiation Therapy Works Only in Certain Tumors

Radiation therapy is an important cancer treatment, but its success is not the same for everyone. Even patients with the same type of cancer can respond differently, making it difficult to predict who will benefit. Understanding why some tumors are sensitive to radiation while others resist it is key to improving treatment and patient survival.

The Results: Radiation Therapy Works for Glioblastoma but Not for Low-Grade Gliomas

Overall, GBM had the highest percentage of patients receiving radiation therapy (82%), followed by LGG (54%). When researchers compared survival outcomes, they found that while radiation improved survival in breast cancer and GBM patients, it had a negative effect on patients with lung adenocarcinoma and LGG. This led researchers to take a closer look at GBM and LGG, especially since LGG can develop into GBM over time.

A key discovery was how GBM and LGG regulate DNA repair differently. GBM tumors have weak DNA repair activity, making them more vulnerable to radiation-induced damage. LGG tumors, however, activate more DNA repair pathways, allowing cancer cells to survive radiation and potentially making treatment less effective.

The immune response to radiation therapy was also different. In GBM, radiation triggered an immune response, which may help fight the tumor. In LGG, however, immune activation was significantly lower, meaning that radiation therapy did not enhance the body’s ability to attack cancer cells. This fact may contribute to worse survival outcomes for LGG patients after treatment.

Further genetic analysis revealed that ATRX gene mutations made GBM and LGG patients more sensitive to radiation. On the other hand, higher EGFR gene activity was linked to lower survival rates after radiation in LGG patients. Similar findings for GBM tumors indicate treatment resistance.

The Breakthrough: Toward Personalized Treatment

This study offers new insights into why radiation therapy benefits certain brain tumors while being less effective, particularly in GBM and LGG. Finding important biological factors, like DNA repair activity, immune response, and genetic changes that may serve as biomarkers, will help radiation therapy be more precisely tailored to each patient’s unique tumor profile. 

The Impact: Rethinking Glioblastoma and Low-Grade Gliomas Treatment

These findings highlight the importance of precision medicine in brain cancer treatment. Instead of automatically recommending radiation therapy for all LGG patients, oncologists should consider genetic testing to determine whether this treatment will be beneficial or not. If not, alternative treatments may be necessary. Immunotherapy and targeted drugs against EGFR could provide better outcomes for patients who do not respond well to radiation therapy.

For GBM, researchers are investigating ways to enhance radiation’s effectiveness by combining it with DNA repair inhibitors, such as PARP inhibitors. These drugs could increase tumor sensitivity to radiation and improve survival rates. 

Conclusion

Advancing cancer treatment requires a personalized approach. Identifying biomarkers that predict how GBM and LGG tumors respond to radiation therapy can help clinicians make more informed treatment decisions, ensuring that patients receive the most effective and least harmful therapies. By uncovering key genetic and molecular insights, this study moves the field closer to individualized brain cancer treatments, improving survival rates while reducing unnecessary risks for patients.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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A New Approach to Healing Aging Skin: Insights from Senolytic Research

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“Senescent cells accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury.”

Imagine a simple topical treatment that could help aging skin heal faster, reducing recovery time from wounds and even improving skin quality. Scientists may have found exactly that. A recent study, published in Aging, reveals that a compound called ABT-263 can eliminate aging cells in the skin, boosting its ability to regenerate. 

Understanding How Aging Affects Skin Healing

Aging affects the skin’s structure and function, leading to a reduced ability to heal from wounds. Scientists have long suspected that senescent cells, also known as “zombie cells,” play a major role in this decline. These cells stop dividing but refuse to die, accumulating in tissues and releasing inflammatory molecules that impair the body’s natural repair processes.

Various studies have explored senolytics, a class of drugs designed to eliminate these aging cells and restore tissue function. While these drugs have shown promise in treating diseases like osteoporosis and fibrosis, their impact on skin regeneration and wound healing has been less studied. A new study titled “Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing” now suggests that a topical application of the senolytic ABT-263 could significantly improve wound healing in older individuals.

The Study: How Clearing Aging Cells Improves Skin Repair

A team of researchers from Boston University Aram V. Chobanian and Edward Avedisian School of Medicine, led by first author Maria Shvedova and corresponding author Daniel S. Roh, tested whether ABT-263 could enhance wound healing in aging skin. They applied topical ABT-263 to the skin of 24-month-old mice—roughly equivalent to elderly humans—over a five-day period. After the treatment period, the researchers created small skin wounds on the mice and monitored their healing process compared to a control group. They also analyzed molecular changes in the skin to understand how the drug influenced tissue repair.

The Challenge: Why Aging Skin Heals More Slowly

Older skin does not regenerate as well as younger skin due to a combination of factors. One key reason is the accumulation of senescent cells, which interfere with normal repair processes by increasing inflammation and reducing collagen production, a critical component of wound healing.

Even though the body has mechanisms to remove damaged cells, these processes weaken with age. As a result, senescent cells accumulate, contributing to chronic inflammation that delays wound closure.

The Results: Faster Healing and Improved Skin Function

The study found that topical ABT-263 effectively reduced the number of senescent cells in aged skin. Markers of cellular aging were significantly decreased, confirming that the drug successfully eliminated dysfunctional cells.

When wounds were induced after treatment, mice that received ABT-263 healed significantly faster than those in the control group. The researchers also observed an increase in gene activity related to collagen production, cell proliferation, and extracellular matrix organization—all crucial factors for effective wound repair.

Interestingly, the treatment triggered a temporary inflammatory response, with immune cells, particularly macrophages, infiltrating the treated skin at higher levels. This response, while short, appeared to accelerate repair by clearing out damaged tissue and promoting regeneration.

By day 15, the wounds of ABT-263-treated mice had closed significantly faster than those of untreated mice. By day 24, 80% of the treated mice had achieved complete wound closure, compared to only 56% in the control group.

The Breakthrough: A New Approach to Enhancing Skin Regeneration

This study provides strong evidence that removing senescent cells before an injury can prime aging skin for faster healing. The results suggest that topical senolytic drugs like ABT-263 could serve as a pre-treatment for surgeries or individuals prone to slow-healing wounds, providing a safer, more targeted approach than systemic treatments. Additionally, the observed increase in collagen expression suggests that this method not only accelerates healing but also improves the overall strength and quality of repaired skin.

The Impact on Wound Care and Skincare

If similar results can be achieved in humans, ABT-263 or similar senolytic treatments could become valuable tools, particularly for elderly patients undergoing surgery, where slow wound healing increases the risk of complications. It may also help individuals with chronic wounds, such as diabetic ulcers, which often struggle to heal properly. In post-surgical skincare, accelerating recovery could lead to better outcomes and reduced scarring. Additionally, in anti-aging dermatology, this treatment has the potential to reverse some of the cellular effects of aging on the skin.

​​Future Prospects and Conclusion

This study marks an important step toward clinical applications. While the findings are promising, further research is necessary to confirm whether ABT-263 offers similar benefits in humans. Clinical trials will be crucial in assessing its safety, efficacy, and long-term effects, particularly in wound healing and dermatological treatments. If successful, senolytic creams or topical therapies could offer new solutions for age-related skin challenges and slow-healing wounds.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Click here to subscribe to Aging publication updates.

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How Scientists Are Measuring Aging at the Cellular Level

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“We illustrate our strategy in brain and liver tissue, demonstrating how cell-type specific epigenetic clocks from these tissues can improve tissue-specific estimation of chronological and biological age.”

Aging affects everyone differently. There are two types of aging: chronological aging, which refers to the number of years a person has lived, and biological aging, which reflects how well the body is functioning based on cellular changes. A recent study published as the cover for Volume 16, Issue 22 of Aging reports a new discovery that could revolutionize the way we understand aging and its impact on health. 

Understanding Biological Age

Biological age reflects how well the body is aging and can vary based on lifestyle, genetics, and environmental factors. Traditionally, scientists estimate it using epigenetic clocks, which measure DNA methylation, chemical changes that occur over time. Until recently, these clocks could only provide general estimates by analyzing entire tissues, meaning they could not distinguish how different cell types aged within those tissues. A recent study titled “Cell-type Specific Epigenetic Clocks to Quantify Biological Age at Cell-Type Resolution” aims to change that.

The Study: Measuring Aging More Precisely

To explore how different cell types age, researchers from the Chinese Academy of Sciences and Monash University analyzed publicly available DNA methylation data from brain and liver tissues using advanced computer models. The samples included healthy individuals and those with diseases like Alzheimer’s and non-alcoholic fatty liver disease. 

In addition to brain and liver samples, the study included data from other tissues such as the prostate, colon, kidney, and skin. This broader dataset ensured that the findings applied to a wide range of conditions.

The Challenge: Understanding Aging at a Cellular Level

One of the biggest challenges in estimating biological age has been the inability to distinguish between different cell types within a tissue. Traditional methods analyze a tissue as a whole, averaging the age of all existing cells. This can hide the fact that some cells age faster than others, making it difficult to identify early signs of disease.

In organs like the brain and liver, different cell types—such as neurons and glial cells in the brain, or hepatocytes in the liver—age at different rates. Without a method to study cell types individually, it has been challenging to identifying which cells are most affected by aging and how they contribute to diseases like Alzheimer’s and liver diseases.

Aging is also influenced by two factors: intrinsic aging, which refers to changes within the cells themselves, and extrinsic aging, which occurs due to changes in cell composition within a tissue. Traditional methods struggle to separate these aspects, limiting their usefulness in developing targeted anti-aging treatments.

The Results: Key Findings in Alzheimer’s and Liver Disease

The study found that different types of cells within the same tissue age at different rates. In Alzheimer’s disease, neurons and glial cells in the brain showed signs of accelerated aging, with glial cells in the temporal lobe being the most affected. This suggests that glial cells could play a crucial role in the progression of neurodegeneration. Similarly, in liver conditions such as fatty liver disease and obesity, hepatocyte-specific clocks detected signs of accelerated aging that were not as easily identified previously.

By applying their approach to brain and liver tissues, the researchers demonstrated that cell-type specific epigenetic clocks can improve tissue-specific estimation of biological age, as well as chronological age.

The Breakthrough: Cell-Type Specific Epigenetic Clocks

Before this study, biological age could only be estimated at the tissue level, providing a general picture but not showing how individual cell types were changing over time. With the development of cell-type specific epigenetic clocks, researchers can now measure aging within specific types of cells, such as neurons in the brain and hepatocytes in the liver. Also, by distinguishing intrinsic aging from changes in cell composition, this new method offers new insights into how diseases develop and progress.

The Impact: What This Means for Healthcare

The implications of this research are significant. Measuring the biological age of individual cell types can lead to earlier diagnosis of age-related diseases, more effective treatments, and personalized healthcare plans. It could also help scientists track the effectiveness of anti-aging therapies and lifestyle changes more accurately, giving individuals better tools to manage their health.

This research also offers valuable insights into age-related conditions like Alzheimer’s and liver diseases, by pinpointing which cells experience the most stress and deterioration, allowing researchers to focus their efforts on the most affected cell types.

​​Future Prospects and Conclusion

Looking ahead, researchers plan to use this method to study other tissues and cell types, further advancing the field of precision medicine. As more data becomes available, cell-type specific epigenetic clocks could become essential tools for tracking aging at an individual level.

This study represents an exciting step forward in the science of aging. By measuring aging at the cellular level, scientists are moving closer to a future where aging can be better understood and managed.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Click here to subscribe to Aging publication updates.

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Exploring Baseline Variations and Mechanical Loading-Induced Bone Formation in Young-Adult and Aging Mice through Proteomics

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Bone mass declines with age, and the anabolic effects of skeletal loading decrease. While much research has focused on gene transcription, how bone ages and loses its mechanoresponsiveness at the protein level remains unclear.

Researchers Christopher J. Chermside-Scabbo, John T. Shuster, Petra Erdmann-Gilmore, Eric Tycksen, Qiang Zhang, R. Reid Townsend, Matthew J. Silva from Washington University School of Medicine and Washington University in St. Louis, MO, share their findings which underscore the need for complementary protein-level assays in skeletal biology research.

On October 12, 2024, their research paper was published as the cover of Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science), Volume 16, Issue 19, entitled, “A proteomics approach to study mouse long bones: examining baseline differences and mechanical loading-induced bone formation in young-adult and old mice.”

THE STUDY

In this study, the tibias of young-adult and old mice were analyzed using proteomics and RNA-seq techniques, while the femurs were examined for age-related changes in bone structure. A total of 1,903 proteins and 16,273 genes were detected through these analyses. Multidimensional scaling demonstrated a clear separation between the young-adult and old samples at both the protein and RNA levels. Furthermore, 93% of the detected proteins were also identifiable by RNA-seq, and the abundance of these shared targets showed a moderately positive correlation. Additionally, differential expression analysis revealed 183 age-related differentially expressed proteins and 2,290 differentially expressed genes between young-adult and old bone samples.

Proteomic and RNA-seq analyses were conducted on paired tibias from young-adult and old mice to study age-related differences and the effects of mechanical loading on bone formation. The results showed distinct differences in protein and gene expression between the two age groups. Many of the significantly upregulated and downregulated proteins and genes in old bone have been associated with bone phenotypes in genome-wide association studies (GWAS). The study also identified age-related differentially expressed proteins and genes involved in bone phenotypes and aging processes. Integrated analysis with GWAS data revealed eight targets that may be relevant to human disease, including Asrgl1 and Timp2. Furthermore, co-expression analysis identified an age-related module indicating baseline differences in TGF-beta and Wnt signaling. Baseline age-related differences in ECM/MMPs and TGF-beta signaling were detected in both the proteome and transcriptome. Following mechanical loading, the proteome showed distinct pathway, protein class, and process enrichments, with temporal differences observed between young-adult and old mice.

Overall, the findings provide valuable insights into the molecular mechanisms underlying age-related changes and the response to mechanical loading in mouse long bones.

DISCUSSION

This study aimed to compare the proteome and transcriptome of tibias from young-adult and old mice under baseline conditions and analyze changes in the bone proteome in response to mechanical loading. The researchers successfully developed a proteomics method to detect protein-level changes in cortical bone and used it to perform proteomic and RNA-seq analyses on tibias from both young-adult and old mice. They observed a moderately positive correlation between the proteome and transcriptome in bone tissue. Age-related differences were detected at both the protein and RNA levels, with altered TGF-beta signaling and changes in extracellular matrix (ECM) and matrix metalloproteinases (MMPs) protein and transcript levels in old bones. The researchers identified Tgfb2 as the most reduced Tgfb transcript in old bone, predominantly expressed by osteocytes. Proteomic analysis of the loading response showed modest changes compared to age-related differences, with fewer protein-level changes in old bones. The findings suggest that proteomics is a valuable tool for studying bone biology and can provide insights into protein-specific changes in aging.

The data obtained from the analysis were subjected to various statistical and data exploration techniques. Differential expression analysis was performed to compare protein abundance between different groups. Total RNA was extracted from the bones using TRIzol, and its integrity and concentration were measured. The bones were also processed for paraffin sectioning and RNA in situ hybridization.

Overall, the study involved the collection and analysis of bone samples from female mice to investigate age-related changes and loading responses in the skeletal system.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Click here to subscribe to Aging publication updates.

For media inquiries, please contact [email protected].

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How Single Housing Impacts Growth and Lifespan in African Turquoise Killifish

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“[…] our results suggest that sharing housing with others in early life might influence whole-life attributes, potentially leading to specific life history traits beyond the typical relationship between the growth rate and lifespan.”

In this research, Chika Takahashi, Emiko Okabe, Masanori Nono, Saya Kishimoto, Hideaki Matsui, Tohru Ishitani, Takuya Yamamoto, Masaharu Uno, and Eisuke Nishida from the RIKEN Center for Biosystems Dynamics Research (BDR) in Hyogo, Japan; Brain Research Institute, Niigata University in Niigata, Japan; Research Institute for Microbial Diseases at Osaka University in Osaka, Japan; Kyoto University in Kyoto, Japan; and RIKEN Center for Advanced Intelligence Project (AIP), explored the effects of housing density during the juvenile stage on whole-life traits, including growth, fecundity, and lifespan, in African turquoise killifish. Their research paper was published on the cover of Aging (listed by MEDLINE/PubMed as Aging (Albany NY) and as Aging-US by Web of Science), Volume 16, Issue 18, entitled, “Single housing of juveniles accelerates early-stage growth but extends adult lifespan in African turquoise killifish.”

THE STUDY

A study on African turquoise killifish examined the impact of housing density on juvenile growth. Newly hatched fish were kept in different densities ranging from 1 to 40 fish per tank. It was found that lower housing densities resulted in faster growth, with fish in single housing growing significantly larger than those in group housing. Additionally, single-housed fish reached sexual maturity earlier compared to group-housed fish at higher densities. Comparisons between group-housed and single-housed fish showed that housing conditions in the juvenile stage did not affect the appearance changes during sexual maturation. 

As the fish progressed to middle-aged adults, the rate of increase in body length slowed down, while body weight continued to increase. Differences in body weight between group-housed and single-housed fish persisted into old age, suggesting potential differences in body composition. Surprisingly, single-housed fish had a longer mean adult lifespan compared to group-housed fish, contradicting the commonly held belief that faster growth leads to shorter lifespan. Lower housing densities during the juvenile stage were also found to extend adult lifespan, further challenging the inverse correlation between growth rate and lifespan. These findings suggest that lower housing densities promote accelerated growth in the juvenile stage of African turquoise killifish.

The study also found that single-housed fish had a longer adult lifespan compared to group-housed fish. This led to the suspicion that the egg-laying period of single-housed fish might also be longer. To investigate this, the researchers conducted weekly monitoring of the number of eggs laid until the old adult stage. In group-housed fish, the number of eggs laid was high for the first two weeks, followed by a medium level for the subsequent five weeks, and then decreased. In contrast, single-housed fish showed a medium level of egg-laying for the first nine weeks, followed by a decrease. The cumulative number of live embryos was found to be lower in single-housed fish compared to group-housed fish. These findings suggest that while the number of eggs laid is not very high, single-housed fish have a longer egg-laying period than group-housed fish.

To investigate the potential reasons behind the reduction in offspring number and longer egg-laying period in single-housed fish, the researchers conducted RNA sequencing analysis of testes or ovaries at four life stages. These stages included the onset of sexual maturity, young adult, mature adult, and middle-aged adult. Interestingly, the analysis revealed that single-housed fish showed higher similarity to group-housed fish at earlier life stages compared to group-housed fish at the same life stage. For instance, in the testes, single-housed fish at stage II exhibited the highest similarity to group-housed fish at stage I. Similarly, in the ovaries, single-housed fish at stage II and III showed higher similarity to group-housed fish at stage I. These findings suggest that the rate of gonadal transcriptional change with life stage progression is slower in single-housed fish compared to group-housed fish.

The researchers identified differentially expressed genes (DEGs) between stage I and stage IV in group- and single-housed fish. In the testes, ribosome-related genes and cilium-related genes were highly enriched in DEGs with higher expression in stage I compared to stage IV, suggesting a link between life stage progression, testes development, and spermatogenesis. In the ovaries, growth-related genes and translation-related genes were highly enriched in DEGs with higher expression in stage I compared to stage IV, indicating a link between life stage progression, ovarian development, oogenesis, and aging. Comparing group-housed and single-housed fish at different stages, there were differences in the PC1 values, suggesting that single-housed fish exhibited slower progression of gametogenesis and gonadal maturation relative to life stage progression compared to group-housed fish.

To further investigate this, the researchers focused on specific genes related to spermatogenic differentiation, oocyte development, oocyte construction, and female gonad development. The expression of these genes showed slower changes with life stage progression in single-housed fish compared to group-housed fish in both the testes and ovaries. This suggests that single-housed fish may have slower rates of gametogenesis and gonadal maturation, leading to a lower proportion of mature sperm and oocytes in their gonads. Overall, the results indicate that, at the transcriptional level, the progression of gonadal maturation and ovarian aging is slower in single-housed fish compared to group-housed fish. This slower progression may explain the medium fecundity and extended egg-laying period observed in single-housed fish.

The liver was chosen for analysis as it plays a central role in organismal metabolic processes. Gene expression profiles of the livers were compared between group- and single-housed fish at two different ages: 7 weeks post-hatching (wph) and 14 wph. Surprisingly, despite the 2-week age difference, the correlation coefficients showed that group- and single-housed fish at 14 wph were highly similar. The researchers identified 1588 age-related differentially expressed genes (DEGs) between the two age groups. Hierarchical clustering based on the expression changes of these age-related genes demonstrated that the expression profiles of group- and single-housed fish were similar at 14 wph.

IN CONCLUSION

In summary, juvenile single housing in African turquoise killifish promotes faster growth, longer egg-laying periods, and extended lifespans compared to group housing. These findings challenge traditional assumptions about the relationship between growth and lifespan and shed light on the impact of early-life environmental conditions on overall life history.

Overall, the experiments involved maintaining and rearing the fish, measuring their body length and weight, analyzing RNA sequencing data, measuring lifespan, and counting the number of eggs laid. Statistical analysis was conducted to assess significant differences between groups.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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The Cell Rejuvenation Atlas: Unveiling Rejuvenation Strategies through Network Biology

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Researchers introduce SINGULAR, a cell rejuvenation atlas that provides a unified analysis framework to study the effects of rejuvenation strategies at the single-cell level.

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Researchers Javier Arcos Hodar, Sascha Jung, Mohamed Soudy, Sybille Barvaux, and Antonio del Sol from CIC bioGUNE-BRTA and University of Luxembourg introduce SINGULAR, a cell rejuvenation atlas that provides a unified analysis framework to study the effects of rejuvenation strategies at the single-cell level. On September 9, 2024, their research paper 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 17, entitled, “The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies.”

THE RESEARCH

Various strategies, including lifestyle changes, gene therapies, and surgical procedures, have shown promise in improving aging markers and increasing lifespan in model organisms. These interventions often have limitations, however, such as not achieving comprehensive functional improvement across tissues or facing challenges in clinical translation. To address these limitations, the researchers characterized and compared rejuvenation interventions at different biological levels. The paper introduces SINGULAR, a cell rejuvenation atlas that provides a unified analysis framework to study the effects of rejuvenation strategies at the single-cell level. By examining gene regulatory networks, intracellular signaling, cell-cell communication, and cellular processes, the atlas identifies master regulators and common targets across immune cells. SINGULAR has the potential to inform future advancements in human age reversal and aid in the selection of drugs that mimic the effects of rejuvenation interventions.

RESULTS

The authors propose a unified multiscale analysis pipeline for characterizing and comparing the effects of rejuvenation interventions. This process begins by filtering low-quality cells, normalizing expression profiles, and identifying optimal cell clustering. The data is then analyzed at various biological levels, including differential gene expression, transcriptional regulatory networks, signaling cascades, and intercellular communication.

Nine previously published single-cell RNA-seq datasets from different rejuvenation interventions were collected and analyzed, revealing technical variability that highlights the need for a standardized data processing pipeline. The analysis showed heterogeneous gene expression responses across different cell types and organs. Systemic interventions had consistent effects on multiple organs, while metformin had minimal impact. Interestingly, exercise produced the largest transcriptional effects in the liver, artery, and spinal cord, even though it primarily targets muscles.

Transcriptional regulatory networks (TRNs) were reconstructed to explore the regulatory mechanisms behind these gene expression changes. The TRNs, which averaged 72 genes, were highly hierarchical, indicating the presence of ‘master regulators’ that explain significant portions of gene expression changes.

To demonstrate the practical application of SINGULAR, the study investigated the identification of drugs that could target transcription factor (TF) master regulators and key signaling molecules. Drug-target relationships from DrugBank were analyzed to find drugs that could activate master regulators or mimic the effects of rejuvenation interventions. Interestingly, only 17 out of 239 TFs could be activated by drugs, primarily nuclear receptors, with notable exceptions like AP-1 complex proteins and Trp53. Some of these drugs, such as Curcumin and Vitamin D3, have shown rejuvenating effects on lifespan in model organisms. Key signaling molecules were found to be more druggable, with several drugs targeting specific molecules, though none targeted both genes.

The study aimed to identify master regulators and their downstream effects in rejuvenation interventions. By simulating the activation of transcription factors (TFs) within the network, the researchers quantified the number of genes regulated by each TF. They discovered 493 TFs with non-zero activity across various conditions, though most acted as master regulators in only a few cases. The study also highlighted key differences between TFs involved in aging-related activity changes and those regulating rejuvenation. Notably, the AP-1 complex, consisting of Fos and Jun, emerged as a common master regulator across multiple interventions. The researchers also identified TFs linked to aging and validated their potential rejuvenating effects experimentally. They also explored crosstalk between TFs and signaling pathways, finding negative enrichment of aging gene sets in several integrated networks. Overall, the findings offer valuable insights into the regulatory mechanisms and potential rejuvenating effects of master regulators and signaling molecules involved in rejuvenation interventions.

CONCLUSION

In conclusion, this study employed a unified analysis pipeline, SINGULAR, to compare the effects and mediators of various rejuvenation interventions. Key master regulators, including Arntl, AP-1 complex proteins, NFE2L2, and MAF, were identified as playing crucial roles in rejuvenation. The analysis revealed distinct differences between aging-related transcriptional changes and rejuvenation regulators. Immune and skin cell types were highlighted as potential intervention targets, with the possibility of additive or synergistic effects by targeting non-overlapping master regulators. Some limitations were noted, such as biases in cell type comparisons, reliance on ligand-receptor interactions for cell-cell communication analysis, and the risk of false negatives in differential expression testing. Despite these limitations, SINGULAR offers valuable insights into rejuvenation mechanisms and the identification of agents for anti-aging strategies. It provides a robust framework for understanding the mechanisms behind various interventions and offers a wide range of potential target genes for a comprehensive anti-aging approach.

Click here to read the full research paper in Aging.

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Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

Click here to subscribe to Aging publication updates.

For media inquiries, please contact [email protected].

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Unveiling Role of Cytoskeleton in Aging: Insights from Dermal Fibroblast Research

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In this study, researchers reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.

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Dermal fibroblasts orchestrate the synthesis and degradation of extracellular matrix components, which is crucial for skin homeostasis. Alterations in the expression of components such as collagens and enzymes can lead to reduced mechanical cutaneous tension and impaired skin wound healing during aging.

Researchers Françoise Boismal, Sandy Peltier, Sophie Ly ka so, Guillaume Chevreux, Loïse Blondel, Kévin Serror, Niclas Setterblab, Elina Zuelgaray, David Boccara, Maurice Mimoun, Christelle Guere, Armand Benssussan, Marie Dorr, Gallic Beauchef, Katell Vie, and Laurence Michel from Saint-Louis Hospital, Paris; Paris University, Paris Cité; Jacques-Monod Institute, Paris; and Clarins Laboratories, Pontoise, aimed to better understand the molecular alterations in fibroblasts during aging by comparing secretomic and proteomic signatures of fibroblasts from young (<35years) and aged (>55years) skin donors, in quiescence or TGF-stimulated conditions, using HLPC/MS. 

Their research paper was published on the cover of Aging’s Volume 16, Issue 16, entitled, “Proteomic and secretomic comparison of young and aged dermal fibroblasts highlights cytoskeleton as a key component during aging.”

Dermal fibroblasts were obtained from healthy, sun-protected skin of young (<35 years) and aged (>55 years) healthy women undergoing breast reduction surgery. Peptides were loaded using an online preconcentration method and separated by chromatography. RNA extraction, reverse transcription, quantitative PCR, and blot quantification were performed, along with immunostaining on fibroblasts seeded on culture chamber slides.

To identify key molecules involved in the role of human dermal fibroblasts during wound healing and skin aging, a comparative analysis of the secretome and proteome of 12 fibroblast cultures, freshly isolated from young and mature skin, was conducted using HPLC/MS. This analysis was performed in both quiescence and TGF-β1-treated conditions, without senescence-inducing factors, as described in previously reported aging models. Importantly, the analyses were conducted in the absence of serum in the culture medium 24 hours before and during cell stimulation to avoid serum protein contamination in the secretomic and proteomic assays

This study revealed a significant decrease in fibroblast protein secretion with age, while cytoplasmic protein accumulation increased by over 60%. Proteins related to actin and ECM (extracellular matrix) organization were the two main categories altered during aging. An in-depth analysis of actin-related proteins highlighted the involvement of CFL1, CORO1C, the ARP2/3 complex, FLNB, and ACTC1 in cytoskeleton organization and fibroblast migration. These findings offer potential new targets to slow key features of skin aging.

“Our present data reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.”

Read the full research paper, published in Aging.

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Aging is an open-access, traditional, peer-reviewed journal that publishes high-impact papers in all fields of aging research. All papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

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