The disposable soma theory and expensive germline hypothesis

Reproduction is an energetically costly process that has profound effects on metabolism. The disposable soma theory of aging and expensive germline hypothesis state that organisms age due to an evolutionary trade-off between reproduction and DNA repair / maintenance. Formulated by the biologist Thomas Kirkwood, the disposable soma theory explains that an organism only has a limited amount of resources that it can allocate to its various cellular processes. Therefore, a greater investment in reproduction would result in reduced investment in DNA repair and maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence.

Reproduction inhibits lifespan with regard to multicellular organisms. With regards to cellular replication, the progressive shortening of telomeres is a mechanism which limits the amount of generations a single cell may undergo. Furthermore, in unicellular organisms like Saccharomyces cerevisiae, the formation of extrachromosomal rDNA circles (ERCs) in mother cells (but not daughter cells) upon every subsequent division is an identifiable type of DNA damage that is associated with replication. These ERCs accumulate over time and eventually trigger replicative senescence and death of the mother cell. Additionally, it has been found that reproduction alters the metabolism of fat. The lipids invested in reproduction would be unavailable to the mechanisms involved in somatic maintenance.

The disposable soma theory has been consistent with the majority of animal models. It was found in numerous animal studies that castration or genetic deformities of reproduction organs was correlated with increased lifespan. Moreover, in red squirrels, it was found that females with an early primiparity achieved the highest immediate and lifetime reproductive success. However, it was also found that these same individuals had a decreased median and maximum lifespan. Specifically squirrels who mated earlier had a 22.4% rate of mortality until two years of age compared to a 16.5% rate of mortality in late breeders. In addition, these squirrels had an average maximum lifespan of 1035 days compared to an average maximum lifespan of 1245 days for squirrels that bred later.

In another study, researchers selectively bred fruit flies over three years to develop two different strains, an early-reproducing strain and a late-reproducing strain. The late-reproducing line had a significantly longer lifespan than the early-reproducing line. Even more telling was that when the researchers introduced a mutation in the ovarian-associated gene ovoD1, resulting in defective oogenesis, the differences in lifespan between the two lines disappeared. The researchers in this case concluded that "aging has evolved primarily because of the damaging effects of reproduction earlier in life".

Prominent aging researcher Steven Austad also performed a large-scale ecological study on the coast of Georgia in 1993. Austad isolated two opossum populations, one from the predator-infested mainland and one from the predator-absent nearby island of Sapelo. According to the disposable soma theory, a genetically isolated population subject to low environmentally-induced mortality would evolve delayed reproduction and aging. This is because without the pressure of predation, it would be evolutionarily advantageous to allocate more resources to somatic maintenance than reproduction, as early offspring mortality would be low. As predicted, even after controlling for predation, the isolated population had a longer lifespan, delayed primiparity, and reduced aging biomarkers such as tail collagen cross-linking.

Recent evidence suggests that the three processes might be causally linked through a reproductive–endocrine signalling axis. In the nematode C. elegans and the fruit fly Drosophila melanogaster, for example, ablation of the germline increases lifespan (Flatt et al., 2008; Hsin and Kenyon, 1999) and significantly alters lipid metabolism (O'Rourke et al., 2009; Parisi et al., 2010). Moreover, studies in C. elegans have begun to uncover the molecular mechanisms by which signals from the reproductive system regulate lipid metabolism and lifespan (Goudeau et al., 2011; Lapierre et al., 2011; McCormick et al., 2011; Wang et al., 2008).

The effect of germline ablation on longevity was also examined in D. melanogaster. The idea of this was based on the study of sterile grandchildless mutants of D. subobscura and the finding that such mutants had an extended lifespan. The ablation of the germline resulted in an increase in lifespan by 31.3% to 50% in females and 21% to 27.8% in males. Also observed was that germ cell overproliferation shortens the life of the organism. Aging delay and increased lifespan was due to the elimination of metabolic demands required to produce gametes, as a result of the removal of the germline.

As for the human models, it was found that castrated men live longer than their fertile counterparts. Further studies found that in British women, primiparity was earliest in women who died early and latest in women who died at the oldest ages. Furthermore, increased number of children birthed was associated with a decreased lifespan. A final study found that female centenarians were more likely to have children in later life compared average, especially past the age of 40. The researchers discovered that 19.2% of female centenarians had their first child after the age of 40, compared to 5.5% of the rest of the female population.

To sum up, the body can either prioritize reproduction or maintenance / regeneration not both processes simultaneously. Reproduce on a regular basis and your body will deteriorate. Stop reproducing and your body's maintenance / regeneration will become the priority.

Disposable soma theory and expensive germline hypothesis:







Currently it is one of the main theories of ageing. There are numerous studies validating it experimentally in a number of living organisms. Below are some of the studies:

• https://onlinelibrary.wiley.com/doi/abs/10.1111/ele.13593
• https://pubmed.ncbi.nlm.nih.gov/32245815/
• https://www.pnas.org/doi/10.1073/pnas.1918205117
• https://www.hfsp.org/hfsp-news-events/expensive-germline-ageing-and-hidden-costs-reproduction
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567776/
• https://pdfs.semanticscholar.org/c8a2/e460d19585931531783a9f7264ecb8f64943.pdf