With the rapid aging of the world’s population, sarcopenia—a condition impacting millions of elderly individuals, significantly affecting their quality of life—has become a pressing public health concern. Recently, scientists have identified a protein that could play a crucial role in new therapies for muscle loss due to aging and cancer, potentially improving quality of life.
As the global population continues to age, sarcopenia, which impacts millions of seniors and greatly reduces their quality of life, is becoming an urgent public health dilemma. A groundbreaking discovery by researchers at Duke-NUS Medical School may pave the way for enhanced treatments for this condition.
According to a study published in the journal Autophagy, researchers found that maintaining optimal levels of a specific protein, known as DEAF1 (Deformed epidermal autoregulatory factor-1), is essential for muscle repair and regeneration—processes that often decline due to aging or diseases such as cancer. This finding could lead to novel treatments for muscle degenerative conditions like sarcopenia and cachexia.
The research emphasized the significance of muscle stem cells, which are vital for repairing and regenerating muscle tissues. These specialized cells replace muscle damaged by injury or stress, but their effectiveness declines with age, contributing to the muscle loss observed in sarcopenia.
In their investigation of DEAF1’s role in muscle stem cell function and regeneration, the researchers discovered that DEAF1 governs autophagy, an essential process for cells to clear out and recycle damaged elements. Effective autophagy is crucial for maintaining muscle health, and the study indicates that DEAF1 plays a key role in this process.
Dr. Goh Kah Yong, a Research Fellow in the Cancer & Stem Cell Biology Programme at Duke-NUS and co-first author of this study alongside Duke-NUS PhD candidate Ms. Lee Wen Xing, elucidated:
“If DEAF1 levels are too high or too low, it disrupts this essential clean-up activity within our cells. High DEAF1 levels hinder autophagy, leading to the accumulation of damaged proteins within muscle stem cells, which can result in cell death. Conversely, low DEAF1 levels can increase autophagy excessively, hindering muscle cells’ ability to repair and survive. Thus, maintaining a proper level of DEAF1 is crucial for muscle health and effective regeneration.”
While aging impairs muscle repair and upkeep, reducing DEAF1 levels might restore equilibrium by enhancing cellular clearance, thereby boosting muscle stem cell viability and generating new muscle tissue. This approach could mitigate some negative impacts of aging on muscle tissue, potentially lowering muscle loss and promoting overall muscle health. Such treatment would adjust DEAF1 to favorable levels for older adults battling sarcopenia, a widespread condition linked with aging that involves gradual loss of muscle mass and strength.
Sarcopenia notably impacts one’s capacity to perform daily tasks, limiting mobility and independence. Furthermore, it increases the risk of falls and fractures, enhancing general frailty.
Assistant Professor Tang Hong-Wen from the Cancer and Stem Cell Biology Programme at Duke-NUS, who is the study’s senior author and the first recipient of the Diana Koh Innovative Cancer Research Fund award, mentioned:
“Both DEAF1 and muscle stem cells are managed by a family of proteins known as FOXOs. In muscle stem cells, FOXOs are critical regulators of DEAF1 levels, which is vital to maintaining a balance in autophagy.”
However, FOXO function may decrease with age, disrupting DEAF1 levels and leading to compromised muscle repair and regeneration. Interestingly, early-stage experiments using FOXO activators have shown promise in restoring DEAF1 balance and enhancing muscle regeneration, particularly in older individuals.
Addressing Cachexia-Related Muscle Loss
Strategies to modify DEAF1 levels may also provide relief for cancer patients dealing with cachexia, a serious condition marked by noticeable muscle wasting. Unlike sarcopenia, which is associated with aging, cachexia is linked to chronic diseases such as cancer and operates through different biological mechanisms. Therefore, treatment approaches should target the unique biological pathways relevant to each condition.
The research revealed that higher levels of FOXO proteins in cachexia lead to decreased DEAF1 levels, subsequently stimulating autophagy. However, while increased autophagy might aid muscle repair in sarcopenia, it exacerbates muscle loss in cachexia. Thus, in cachexia cases, upping DEAF1 levels could slow down muscle degradation, improving patient outcomes and quality of life.
Even though muscle loss occurs in both sarcopenia and cachexia, the core mechanisms behind these conditions are entirely different.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, remarked:
“It’s vital to understand these differences for creating targeted therapies that focus specifically on the underlying causes of muscle loss in various conditions. As the global population ages and chronic diseases like cancer rise, this understanding will be crucial for enhancing health outcomes and life quality for those impacted by these challenging situations.”
The researchers are also examining DEAF1’s functions in other tissues, hoping to discover new insights that could lead to innovative treatments for various health issues.
