Disposable soma theory of aging
[1] Formulated by British 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.
Deactivation of FOXO results in an inability to express genes involved in responding to oxidative stress response, such as antioxidants, chaperones, and heat-shock proteins.
[6] Additionally, uptake of IGF-1 stimulates the mTOR pathway, which activates protein synthesis (and therefore growth) through upregulation of the translation-promoting S6K1, and also inhibits autophagy, a process necessary for recycling of damaged cellular products.
However, with regards to cellular replication, the progressive shortening of telomeres is a mechanism which limits the amount of generations of a single cell may undergo.
Furthermore, mice injected with growth hormone have been shown to have progressive weight loss, roughing of the coat, curvature of the spine, enlargement of the organs, kidney lesions and increased cancer risk.
Selectively bred for their small size, smaller dog breeds like the Chihuahua (average lifespan of 15–20 years) have the B/B genotype for the IGF-1 haplotype, reducing the amount of IGF-1 produced.
[15] Recent genomic studies have confirmed that the genes involved in growth hormone uptake and signaling are largely conserved across a plethora of species, such as yeast, nematodes, fruit flies, mice and humans.
[16] These studies have also shown that individuals with Laron syndrome, an autosomal recessive disorder resulting in dwarfism due to defects in growth hormone receptors, have increased lifespan.
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.
Patients with HGPS have cellular defects, specifically in the lamin proteins, which regulate the organization of the lamina and nuclear envelope for mitosis.
[31] A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in the repair processes of non-homologous end joining and homologous recombination.
[34] One of the main weaknesses of the disposable soma theory is that it does not postulate any specific cellular mechanisms to which an organism shifts energy to somatic repair over reproduction.
[3] Critics have pointed out the supposed inconsistencies of the disposable soma theory due to the observed effects of caloric restriction, which is correlated with increased lifespan.
[35] Although it activates autophagy, according to classical disposable soma principles, with less caloric intake, there would less total energy to be distributed towards somatic maintenance, and decreased lifespan would be observed (or at least the positive autophagic effects would be balanced out).
However, Kirkwood, alongside his collaborator Darryl P. Shanley, assert that caloric restriction triggers an adaptive mechanism which causes the organism to shift a higher proportion of resources to somatic maintenance, away from reproduction.
[36] This theory is supported by multiple studies, which show that caloric restriction typically results in impaired fertility, but leave an otherwise healthy organism.
[citation needed] Another primary criticism of the disposable soma theory is that it fails to account for why women tend to live longer than their male counterparts.
[42] After all, females invest significantly more resources into reproduction and according to the classical disposable soma principles, this would compromise energy diverted to somatic maintenance.
In these studies, it was found that reproductive naked mole rats actually show significantly increased lifespans compared to non-reproductive individuals, which contradicts the principles of disposable soma.
[47] Additionally, for the relationship between growth and aging, studies are disproportionately conducted on males, to minimize the hormonal fluctuations that occur with menstrual cycling.
For example, studies have shown that poorer individuals, to whom nutritious food and medical care is less accessible, typically have higher birth rates and earlier primiparity.
