The AgingReG Database of Regulatory Relationships in Aging
The scientific community seeks a complete understanding of the progression of degenerative aging, at the fine-grained level of environmental influences on specific molecular machinery in the cell, by cell type, by cell status, and then how all of those mechanisms interact with one another as they change. It is a vast project, and may well be largely irrelevant to the task of building a first generation of rejuvenation therapies based on what we presently know of the forms of damage and dysfunction that accumulate in cells and tissues with age. If damage can be periodically repaired, then it isn't so important to know what that damage does in fine detail when it is left to accumulate.
Aging and cellular senescence are characterized by a progressive loss of physiological integrity, which could be triggered by aging factors such as physiological, pathological and external factors. Numerous studies have shown that gene regulatory events play crucial roles in aging, increasing the need for a comprehensive repository of regulatory relationships during aging. Here, we established a manually curated database of aging factors (AgingReG), focusing on the regulatory relationships during aging with experimental evidence in humans. By curating thousands of published items in the literature, 2157 aging factor entries (1345 aging gene entries, 804 external factor entries and eight aging-related pathway entries) and related regulatory information were manually curated.
The regulatory relationships were classified into four types according to their functions: (i) upregulation, which indicates that aging factors upregulate the expression of target genes during aging; (ii) downregulation, which indicates that aging factors downregulate the expression of target genes during aging; (iii) activation, which indicates that aging factors influence the activity of target genes during aging and (iv) inhibition, which indicates that aging factors inhibit the activation of target molecule activity, leading to declined or lost target activity. AgingReG involves 651 upregulating pairs, 632 downregulating pairs, 330 activation-regulating pairs and 34 inhibition-regulating pairs, covering 195 disease types and more than 800 kinds of cells and tissues from 1784 published literature studies. AgingReG provides a user-friendly interface to query, browse and visualize detailed information about the regulatory relationships during aging. We believe that AgingReG will serve as a valuable resource database in the field of aging research.