Can We Control Aging and Extend Lifespan?
Aging is the natural process of getting old and is characterized by physiological changes that affect the cardiovascular, osteomuscular, digestive, and urinary systems. Memory and thinking skills, sexuality, and weight are also affected by this process.
However, with the advances in genetic techniques, several research groups have shown that single genes can have a dramatic effect on lifespan [1] [2] [3].
Lessons from Yeast
The fungal family of yeasts is eukaryotic micro-organisms that convert carbohydrates to carbon dioxide and alcohol through fermentation. Because of their eukaryotic cell nature, these micro-organisms are used in research to understand the biology of human biology in detail [4], including the processes of aging and longevity.
A systematic analysis study of viable single gene deletions (loss of gene function) in yeast identified several pathways involved in the regulation of longevity pathways and multiple significantly overrepresented functional processes [5].
Among the identified pathways, the LOS1 pathway is involved in tRNA binding and pre-tRNA splicing and export of mature tRNA from the nucleus to the cytosol.
Transfer RNAs (tRNAs) mainly function as adapter molecules that decode messenger RNAs (mRNAs) during protein translation by delivering amino acids to the ribosome [6] and are strongly associated with aging and longevity, hence, the importance of their regulation by the LOS1 pathway. This pathway is also regulated by Rad53, a molecule involved in DNA damage response [7].
Another important molecule in this process includes the nucleoporin Nup100 that regulates longevity by inhibiting the nuclear export of specific tRNAs. Nup100 is regulated by another pathway involving the mTOR (mechanistic target of rapamycin) that is implicated in the control of cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress [5].
Yeast Identified Longevity Pathways and Diet
Interestingly, some of the above-identified pathways are well-known players in controlling the metabolism of nutrients, mainly protein synthesis [6]. Defects in certain tRNA biogenesis proteins have been shown to cause various human diseases, including cancer, neurological disorders, immunodeficiency, and diabetes mellitus that have considerable effects on longevity [6].
Dietary interventions, including calorie restriction, dietary restriction, and protein restriction, have been shown to affect longevity [8]. For instance, Rad53 and mTOR are both regulated by dietary restriction and are likely to act through mechanisms that influence Los1 localization, a key regulator of tRNA function [5]. Another example is associated with glucose deprivation which may also selectively act on Los1 localization.
Conclusion
The loss of several genes, including the ones that control tRNA function, has been associated with increased longevity. Therapeutic interventions that target these pathways can promote longevity. At the dietary level, calorie restriction, dietary restriction, and protein restriction can also promote longevity by modulating tRNA function through their regulating pathways.
References
