A large portion of the aging research community is engaged in understanding the relationship between the endocrine system and longevity. The endocrine system is an extremely complex web of biochemical interactions, feedback loops, and specialized tissues that controls metabolism and growth. It is highly influential on the longevity of a species or an individual, but understanding this system is a vast and complex undertaking. I have no doubt that researchers will still be toiling at this labor when we're well into the era of tissue engineered replacement organs and early medical nanorobots.
Some differences in life span between species can be ascribed to differences in endocrine configuration:
The complex, highly integrative endocrine system regulates all aspects of somatic maintenance and reproduction and has been widely implicated as an important determinant of longevity in short-lived traditional model organisms of aging research. Genetic or experimental manipulation of hormone profiles in mice has been proven to definitively alter longevity.
Here, we examine the available endocrine data associated with the vitamin D, insulin, glucocorticoid and thyroid endocrine systems of naturally long-living small mammals. Generally, long-living rodents and bats maintain tightly regulated lower basal levels of these key pleiotropic hormones than shorter lived rodents. Similarities with genetically manipulated [mammals] suggest that evolutionary well-conserved hormonal mechanisms are integrally involved in lifespan determination.
Interestingly, scientists in search of the underlying mechanisms of enhanced longevity are linking one of the first discovered longevity mutations - knockout of growth hormone receptors in mice, a large alteration to the function of the endocrine system - with changes in methionine metabolism. Methionine is one of the essential dietary amino acids, and you may recall that we have good reason to think methonine restriction plays a large role in the enhanced longevity provided by calorie restriction. We can speculate - well in advance of a good weight of evidence - that this mechanism might underlie a range of diverse longevity mutations.
Endocrine mutant mice have proven invaluable toward the quest to uncover mechanisms underlying longevity. Growth hormone (GH) and insulin-like growth factor (IGF) have been shown to be key players in physiological systems that contribute to aging processes including glucose metabolism, body composition and cellular protection.
Examination of these mutant mice across several laboratories has revealed that differences exist in both the direction and magnitude of change, differences that may result in variation in life span. Growth hormone receptor knockout mice lack a functional GH receptor, therefore GH signaling is absent. These mice have been shown to lack the heightened oxidative defense mechanisms observed in other GH mutants yet live significantly longer than wild type mice.
In this study, glutathione (GSH) and methionine (MET) metabolism was examined to determine the extent of variation in this mutant in comparison to the Ames dwarf, a mouse that exhibits delayed aging and life span extension of nearly 70%. Components of GSH and MET were altered in [growth hormone receptor knockout mice] compared to wild type controls. The results of these experiments suggest that these pathways may be partially responsible for differences observed in stress resistance and the capacity to respond to stressors, that in the long term, affect health and life span.