Aging Fat Cells Implicated in Insulin Resistance

Expression of the tumor suppressor gene p53 in adipose tissue plays a key role in the development of insulin resistance, new studies in mice and humans reveal.

The findings suggest that aging of fat cells, possibly due to oxidative stress, may be involved in the development of diabetes, “and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes,” Dr. Tohru Minamino of Chiba University Graduate School of Medicine and colleagues in Japan propose.

There is evidence that senescent cells may accelerate the aging process and aging-related disease, Dr. Minamino and his team note. To understand the role of cell senescence in diabetes, the researchers looked at adipose tissue from Ay mice, which are engineered to develop a Type 2 diabetes-like disease.

After 20 weeks on a normal diet, the Ay mice had more reactive oxygen species in their adipose tissue than wild-type mice, as well as senescence-like changes in adipose tissue.

Blocking p53 activity in adipose tissue “markedly ameliorated” these changes, improved the animals’ insulin resistance, and reduced the expression of proinflammatory cytokines, the researchers found. Upregulating the gene triggered inflammation, leading to insulin resistance.

Dr. Minamino and his team also studied visceral adipose tissue from abdominal surgery patients, and found that fat from those who were diabetic showed higher expression of inflammatory cytokines and senescence-like changes similar to those seen in the mice, “suggesting that aging of fat cells has a major role in human diabetes.”

They conclude: “p53 activation in adipose tissue may be a pro-aging signal with a negative influence on longevity, whereas inhibition of cellular aging may become a new strategy for the treatment of diabetes as well as aging and its associated diseases.”