preprints.org > biology and life sciences > anatomy and physiology > doi: 10.20944/preprints202205.0212.v1

Preprint Concept Paper Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 11 May 2022 / Approved: 16 May 2022 / Online: 16 May 2022 (14:02:16 CEST)

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging.

aging; antagonistic pleiotropy; biological constraint; hyperfunction; hypofunction; programmatic aging; trade-off

Biology and Life Sciences, Anatomy and Physiology

* All users must log in before leaving a comment