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BUFFALO, NY- December 19, 2023 – A new #research paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 23, entitled, “Sirtuin 6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes.”

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. In this new study, researchers Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, and Brian O. Diekman from University of North Carolina at Chapel Hill, North Carolina State University, Rush University Medical Center, and Thomas Jefferson University aimed to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). 

“In this study, we use irradiation as an acute model of DNA damage to bring the level of damage to equivalent levels across chondrocytes from donors of various ages.”

After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from young (≤45 years old) as compared to middle-aged (50–65 years old) or older (>70 years old) cadaveric donors. Activation of SIRT6 with MDL-800 improved the repair efficiency, while inhibition with EX-527 reduced the rate of repair and increased the percentage of cells that retain high levels of damage. 

In addition to affecting repair after acute damage, treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of baseline DNA damage. Chondrocytes isolated from the knees of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment. Lastly, treating murine cartilage explants with MDL-800 lowered the percentage of chondrocytes with high p16 promoter activity, which supports the concept that using SIRT6 activation to maintain low levels of DNA damage may prevent the initiation of senescence.

“In conclusion, the findings presented here support the hypothesis that the efficiency of DNA damage repair declines with age in chondrocytes and that SIRT6 activation improves repair both in response to an acute irradiation challenge and in the context of age-related damage accumulation. These results emphasize the critical role of SIRT6 in DNA repair and support further studies investigating the use of MDL-800 (or alternative SIRT6 activators) in mitigating senescence induction and ameliorating OA development.”

DOI - https://doi.org/10.18632/aging.205394

Corresponding author - Brian O. Diekman - bdiekman@email.unc.edu

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Sirtuin 6 Activation Rescues the Age-Related Decline in DNA Damage Repair in Chondrocytes

Osteoarthritis doesn't have to limit your mobility or quality of life. Learn how chiropractic care, nutritional protocols, and advanced DUTCH testing at Dopps Chiropractic in Overland Park can alleviate joint pain, reduce inflammation, and promote cartilage repair. Dr. Rory Dopps shares how spinal alignment and holistic care can support long-term joint health. Tune in for actionable insights and natural solutions for managing osteoarthritis effectively. Learn more at https://www.doppschiropracticop.com

Relieving Osteoarthritis Naturally: Chiropractic and Nutritional Solutions for Joint Health

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adace + croko 🦠

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cartilage

ADACE X CROKO - CARTILAGE (P. Tokarev)

"Cartilage” by Kmyle is taken from the "Boreal EP", set for release on 26 September 2025 on EPM Music.


Following EPM's recent vinyl collaboration with Paris's Yoyaku on Reel By Real's "Surkit – Remixed and Remastered" and the return (this time solo) of Madben for the "Groove On" EP we continue the French touch as Paris-based Kmyle makes his debut release for the label with the "Boreal EP".

Kmyle is a name synonymous with boundless audible exploration, who has etched a lasting mark in the realm of electronic music. His career seamlessly blends magnetic techno, hypnotic rhythms and ethereal melodies, inviting listeners on a transcendent voyage through time and space.

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Premiere: Kmyle - Cartilage [EPM Music]

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Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

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New tracks tagged #Cartilage