Preprint: SIRT6 RNA is generally stable with age and changes differently across cell types in Alzheimer’s disease
Preprint: SIRT6 RNA is generally stable with age and changes differently across cell types in Alzheimer’s disease
In a preprint published on September 7, the authors introduced SIRT6.db, an open database of experiments across six species that links changes in SIRT6 to the activity of other genes. The resource helps researchers assess whether SIRT6 RNA abundance reflects the aging state of cells and tissues.
SIRT6 is a protein in the cell nucleus that helps regulate chromatin, the material in which DNA is packaged. In a study published in May, experimentally increasing SIRT6 levels in the livers of old male mice altered chromatin accessibility and the activity of genes involved in inflammation and metabolism. The abundance of messenger RNA, which carries instructions for making the protein, measures a different aspect of SIRT6 biology.
The authors compiled publicly available experiments in which SIRT6 was inactivated, its levels were increased, or point mutations were introduced into the gene. The response of other genes to SIRT6 inactivation varied across species, tissues, and models. Across independent experiments in humans, mice, and macaques, SIRT6 inactivation most consistently reduced the activity of gene programs associated with mitochondrial function. Mitochondria are cellular structures that obtain energy from nutrients. SIRT6.db stores the underlying data and sample descriptions, allowing these comparisons to be checked independently.
The researchers then examined SIRT6 RNA itself in healthy human tissues from people of different ages. In most tissues, its abundance changed little with age. In skin fibroblasts, a type of connective tissue cell, SIRT6 RNA levels were lower in donors older than 80 years.
Single-cell data from Alzheimer’s disease revealed another difference. SIRT6 RNA levels decreased in neurons from the early stages of the disease, increased in microglia, the brain’s immune cells, and decreased at later stages in astrocytes, which support cells in nervous tissue.
Evaluating SIRT6 as a biomarker of age requires information about the tissue, cell type, and sample condition.