17. Antagonistic Pleiotropy Shapes Lifespan Trade-Offs but Does Not Explain Aging’s Existence

Antagonistic pleiotropy is the concept that alleles or traits favored early in life can be selected even if they carry late-life costs, because selection weakens with age, resulting in aging (19, 33, 34). This concept does not explain the emergence of aging (2, 35). First, as aging has been the original, default state of living systems, transition from nonaging to aging states is extremely rare. Second, antagonistic pleiotropy is not the reason why genes have beneficial functions in early life yet detrimental functions in late life. Instead, all genes and, in fact, all organismal functions have antagonistic pleiotropic properties, regardless of whether the organism ages or not. For example, a particular enzyme has a beneficial function, but the by-products of its catalyzed reaction would accumulate over time contributing to the deleteriome, appearing as a late life deleterious effect (2, 35–37). Another example is the use of oxygen: it is required for respiration, but its use results in reactive oxygen species, thereby leading to increasing oxidative damage. Antagonistic pleiotropy mainly explains why selection cannot optimize maintenance independently of function and reproduction. Traits favored for performance can set architectures and operating conditions that increase damage production or constrain repair throughout life; the cost is typically a gradually increasing burden rather than a discrete late-acting trigger (but there are cases of rapidly increasing burden at the end of life, e.g. salmon, antechinus). Thus, pleiotropy shapes trade-offs between life histories and anti-aging defenses (e.g., it can help explain why an organism lives a short or long life), but aging does not require antagonistic pleiotropy to occur.