How the clock is ticking back in aging fat cells can be a remedy for life-threatening illness

No matter how much we try to combat it, aging is a part of life. High cholesterol, diabetes, and fatty liver, the collection of conditions called lifestyle diseases, all become more common as we get older. Interestingly, however, many of these age-related conditions are caused by changes in adipocytes, the fat cells responsible for conserving too much energy.

Now, in a study published in Nature communication, researchers led by the University of Osaka have just discovered how these changes lead to the onset of lifestyle diseases, with a view to reversing the process.

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

The research team decided to focus on autophagy, the process used by cells to eliminate abnormal 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, such as liver or kidney.

Yamamuro says, “We have previously shown that a protein called Rubicon, which inhibits autophagy, is re-regulated in aging tissues. We hypothesize that Rubicon is likely to accumulate in older adipocytes, decrease autophagic activity and contribute to the onset of metabolism. disturbances. “

Surprisingly, however, the researchers found that Rubicon levels were actually reduced in the adipose tissue of old mice, resulting in increased autophagic activity.

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

“In Rubicon’s absence, we have observed excessive autophagy in adipocytes and a decline in adipocyte function,” explains former author Tamotsu Yoshimori. “As a result, the mice developed life-threatening diseases such as diabetes and fatty liver and had significantly higher cholesterol levels, despite eating the same diet as control animals.”

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

“This is a very exciting discovery with important therapeutic implications,” says Yoshimori. “Because age-dependent loss of adipose Rubicon causes life-threatening diseases through excessive autophagy, inhibition of autophagy in adipocytes may help prevent these preventable and potentially life-threatening conditions.”