Study offers insight into causes of age-related inflammation

Advanced age is associated with chronic tissue inflammation which contributes to many age-related diseases, including heart disease and cancer. 

Senescent cells are a specific type of cell that accumulate in tissue as people age. Two characteristics of senescent cells are enlargement of a part of the cell called the nucleolus and the secretion of chemicals known as the senescence associated secretory phenotype (SASP). 

While the SASP contributes to this chronic inflammatory state - and ultimately to disease, the role of nucleolar enlargement in health and aging is unknown. 

The study, led by researchers at the Institute of Genetics and Cancer, has found that a nucleolar protein called TIF-IA accumulates in senescent cells and in intestinal tissue in multiple mouse models of aging. 

This accumulation is caused by DNA damage, which occurs during senescence and is a common feature of ageing tissue. 

The researchers found that TIF-IA levels in the cell are usually controlled by a protein called p62, which targets TIF-IA for degradation. Upon DNA damage, the interaction between p62 and TIF-IA is lost, which allows TIF-IA to accumulate. 

Using methods that reduce TIF-IA protein, they show that accumulation of this protein is essential for nucleolar enlargement and the SASP. Conversely, they show that artificially increasing TIF-IA levels causes nucleolar enlargement, the SASP and senescence.

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