How Turning Back The Time In Aging Fat Cells May Be A Cure For Lifestyle Diseases

No matter how hard we try to fight it, aging is a part of life. High cholesterol, diabetes and fatty liver disease, all of the conditions called lifestyle diseases, become more and more common as we age. Interestingly, however, many of these age-related conditions are caused by changes inside adipocytes, the fat cells responsible for storing excess energy.

Now, in a study published in Nature’s communications, researchers led by Osaka University have discovered exactly how these changes lead to the onset of lifestyle-related diseases, in an attempt to reverse the process.

“Adipocytes produce hormones and cytokines that regulate the function of other metabolic organs,” says lead author Tadashi Yamamuro. “Age-related changes in adipose tissue lead to metabolic disturbances closely associated with life-threatening cardiovascular disease. However, no one really knows what causes adipocyte dysfunction in aging organisms.”

The research team decided to focus on autophagy, the process used by cells to remove unwanted or dysfunctional cellular components. Previous studies had shown that autophagy plays an important role in the prevention of various age-related disorders and is likely to be involved in the aging process. But most relevant was the finding that autophagy is essential for the normal function and longevity of normal organs, like the liver or kidneys.

According to Yamamuro, “We previously showed that a protein called Rubicon, which inhibits autophagy, is upregulated in aging tissue. We therefore hypothesized that Rubicon likely accumulates in aged fat cells, decreasing autophagic activity and contributing to the development of metabolic disorders. “

Surprisingly, however, the researchers found that Rubicon levels were actually lowered in the fatty tissue of elderly mice, which resulted in increased autophagic activity.

To explore the underlying mechanism, the researchers developed a mouse line in which Rubicon was specifically inactivated in adipose tissue.

“In the absence of Rubicon, we observed excessive autophagy in adipocytes and decreased adipocyte function,” explains lead author Tamotsu Yoshimori. “As a result, the mice developed lifestyle-related diseases such as diabetes and fatty liver disease and had significantly higher cholesterol levels, despite the same diet as the control animals.”

The researchers then identified the specific proteins affected by the increased levels of autophagy, showing that supplementation of these proteins in Rubicon deletion mice restored adipocyte function.

“This is a truly exciting discovery with important therapeutic implications,” says Yoshimori. “Because age-related loss of Fat Rubicon causes lifestyle-related diseases via excessive autophagy, inhibition of autophagy in fat cells may help prevent the onset of these prevalent and potentially deadly. ”