Humans tend to die from cardiovascular aging, while flies tend to die from intestinal aging. The intestines of humans age and become dysfunctional, as they do in flies, of course. But intestinal aging usually isn’t a severe enough cause of issues in and of itself to win out over cardiovascular disease, pulmonary disease, and the other more common causes of death. It may well contribute meaningfully to all of those other causes of mortality! The converse can be said for the aging of the cardiovascular system in flies; the consequences are usually less severe than those of intestinal aging in that species. Nonetheless, researchers spend a good deal of time with flies in the study of intestinal aging, as this review paper makes clear.
Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity.
There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.
