The dissipative mechanisms of oxidative metabolism and their deleterious products (e.g., reactive oxygen species) cause various forms of cellular damages. To counteract the accumulation of damage, organisms have evolved highly efficient repair mechanisms, including oxidant scavenging and damage repair. However, the repair mechanisms require energy. If the energy that could be allocated to repair is otherwise channeled to other biological processes, damage will inevitably accumulate despite the high repair efficiency.

During growth, a considerable amount of metabolic energy is allocated to the biosynthesis of new tissues. Providing this energy entails tradeoffs with the requirements of repair mechanism. Numerous studies have confirmed a positive correlation between biosynthetic rate and oxidative damage level or its proxies, such as declined performance and shortened lifespan.

Many researchers have argued that increased biosynthesis leads to increased metabolism, and the latter is the reason for the increased cellular damage. However, while metabolic and biosynthetic rates are usually positively correlated, in some cases they vary independently or even inversely. Moreover, the same degree of changes in these rates may lead to different amounts of damage. But in most studies the observed changes in cellular damage reflect the combined influences of changes in both metabolic and biosynthetic rates. When these two rates vary separately, collective effects obscure the separate contributions of each rate to cellular damage.

In this project, we aim to disentangle the effects of biosynthetic and metabolic rates on cellular damage. It is widely thought that oxidative metabolism is the major cause of cellular damage. Our preliminary results suggest, however, that the level of cellular damage is more sensitive to changes in biosynthetic rather than metabolic rate. Accordingly, we hypothesize that during growth, variation in the biosynthetic rate is the major cause of variation in the level of cellular damage, while variation in the metabolic rate has only a minimal impact.

We try to test this hypothesis on Manduca sexta larvae (hornworms). M. sexta is a novel and ideal model for this project. Not only does it grows fast and is easy to handle, but also its metabolic and biosynthetic rates can be manipulated separately by environmental factors. Therefore, the contributions of each rate to cellular damage can be evaluated independently.

We rear hornworms with different metabolic rate and biosynthetic rates by manipulating the ambient temperature and food supply level. We measure lipid peroxidation and protein carbonyl as proxies of cellular damage.
Our hypothesis leads to two predictions: 1) when biosynthetic rate is fixed, significant changes in metabolic rate will NOT lead to significant changes in cellular damage; and 2) when metabolic rate is fixed, animals with higher biosynthetic rate will have higher levels of cellular damage. These predictions contradict the conventional belief that cellular damage is strongly influenced by metabolic rate.