The Szilard Hypothesis on the Nature of Aging Revisited

Abstract

This year marks the 50th anniversary of a nearly forgotten hypothesis on aging by Leo Szilard, best known for his pioneering work in nuclear physics, his participation in the Manhattan Project during World War II, his opposition to the nuclear arms race in the postwar era, and his pioneering ideas in biology. Given a specific set of assumptions, Szilard hypothesized that the major reason for the phenomenon of aging was aging hits, e.g., by ionizing radiation, to the gene-bearing chromosomes and presented a mathematical target-hit model enabling the calculation of the average and maximum life span of a species, as well as the influence of increased exposure to DNA-damaging factors on life expectancy. While many new findings have cast doubt on the specific features of the model, this was the first serious effort to posit accumulated genetic damage as a cause of senescence. Here, we review Szilard's assumptions in the light of current knowledge on aging and reassess his mathematical model in an attempt to reach a conclusion on the relevance of Szilard's aging hypothesis today.

Ubiquitin Carboxyl-Terminal Esterase L1(UCHL1)S18Y Polymorphism In Patients With Cataracts

“…Given the complexity of the UPS and its essential functions in all organ systems, it is not surprising that it has been implicated in the pathophysiology of a large number of both congenital and acquired diseases and in the process of ageing itself. 25 , 26 Several polymorphisms of the UPS and associated proteins have been described, the majority of which are disease-promoting. 27 , 28 On the contrary, the p.S18Y polymorphism of the UCHL1 gene appears to confer at least a moderate protection in Parkinson's disease.…”

The Degradation and Aging of Biological Systems as a Process of Information Loss and Entropy Increase

“…However, the key idea underlying this theory, which connects the phenomenon of aging with the accumulation of damage in the genome of the cells of a multicellular organism, has been expressed before. Here, we can mention, for example, the theory of somatic mutations proposed by L. Szilard [31,32].…”

Conceptualizing Biological Aging and Frailty in Orthopaedics

“…The hit theory also applies outside the acute trauma setting, although occurring instead as an accumulation of stressors on the body over time, manifesting as an organic loss of physiologic reserve 39,40 . Unlike the acute setting, however, in which recovery is dependent on resuscitation, combating organic loss of physiologic reserve in the outpatient setting requires prevention.…”