Molecular basis of intrinsic aging and its prevention
Cellular life is maintained by the activity of a plethora of functions that prevent molecular damage from occurring in the first place and repair damaged DNA, proteins and other damaged cellular constituents. The phenomenon of aging arises from the fact such functions are performed by proteins that are themselves subject to damage by oxidative modifications. In the framework of this project, aging is studied as a process of progressive functional degeneracy of nearly all cellular functions due to diminishing protein activity and decreased precision of protein interactions within the cellular proteome caused by accumulation of oxidative damage.
The objective of this project is, by studying robust species, to understand the molecular basis of life’s fragility – the so-called “intrinsic aging” – i.e., the fundamental cause(s) of decay of vital functions.
This includes causes of all manifestations of aging and age-related diseases. The hope is to discover eventually ways of their prevention or delay. The observations of age-related rates of morbidity and mortality in the animal kingdom (5th power of age for human population) suggest that humans and animals possess a fundamental species-specific somatic biological clock related to species’ age at reproduction, metabolism, lifestyle, etc. This “intrinsic aging”, whose chemistry we wish to explore, is a common cause of all major age related diseases (cancer, cardiovascular, neurodegenerative and infectious) and death, usually caused by such diseases.
New methods for quantification of protein oxidation at single cell level need to be developed in order to estimate the real biological age of each individual. Since the oxidation damage rises exponentially with age, prevention of the oxidative damage in human cells obtained by the anti-oxidant molecules from the robust species, is expected to slow down, stop, or even reverse (“rejuvenation”), the aging processes in humans.
The “Biology of Human Destiny” subproject requires the quantification of oxidation of each protein to compare quantitatively large numbers of individuals. The key idea is that the “silent” weaknesses at young age become progressively “loud” due to different burn-out rates (oxidation) of proteins in individuals. This analysis should provide the health-related meaning of human genome diversity. This analysis is also expected to explain, for instance, why some athletes fall victims to disease and death early in their life whereas Winston Churchill, with his unhealthy life style, has lived long lucid life, or why Jeanne Calmant lived 122 years and did not get lung cancer after having been an active smoker over one hundred years. This project is indeed about the biology of human destiny – “good luck or bad luck” encrypted in the genome.
These projects are unusual by their conceptual simplicity and the extent of potential impacts. Indeed, cultural evolution, which defines human species, is about transcending human biology. Here I discuss about an approach of transcending human biology in a most natural way – by applying the knowledge of biology (nature).