Recent Research

L’horloge de la vie

L’horloge de la vie
Je fais l’hypothèse qu’elle repose sur des modifications chimiques des protéines, modifications produites, pour l’essentiel, par oxydation, laquelle altérerait son fonctionnement. Le vieillissement et les maladies qui l’accompagnent seraient les conséquences phénotypiques progressives de l’accumulation du dégât oxydatif ainsi causé aux protéines au cours de la vie. Je discuterai également ici de la prévention des maladies « incurables » liées au vieillissement.

Research at MedILS (Mediterranean Institute for Life Sciences): Scientific Vision and Projects

Research at MedILS (Mediterranean Institute for Life Sciences): Scientific Vision and Projects
Scientific Vision and Projects by cofounders Miroslav Radman and Ivan Matic, March 2015.

Epigenetics of Aging

Epigenetics of Aging
Miroslav Radman, 20/02/2015 Prelude to new project: If the most upstream cause of aging is oxidative protein damage, then oxidative damage to the system of DNA methylation maintenance may be the root cause of cell-transmissible changes in DNA methylation patterns. We need to find out if such epigenetic change is subject to reversion by means other than cell reprogramming.

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Phenotypic and Genetic Consequences of Protein Damage

Anita Krisko

1 Mediterranean Institute for Life Sciences, Split, Croatia, 2 INSERM U1001, Faculté de Médecine, 
Université R. Descartes Paris-5, Paris, France

, Miroslav Radman



Although the genome contains all the information necessary for maintenance and perpetuation of life, it is the proteome

that repairs, duplicates and expresses the genome and actually performs most cellular functions. Here we reveal strong

phenotypes of physiological oxidative proteome damage at the functional and genomic levels. Genome-wide mutations

rates and biosynthetic capacity were monitored in real time, in single Escherichia coli cells with identical levels of reactive

oxygen species and oxidative DNA damage, but with different levels of irreversible oxidative proteome damage

(carbonylation). Increased protein carbonylation correlates with a mutator phenotype, whereas reducing it below wild type

level produces an anti-mutator phenotype identifying proteome damage as the leading cause of spontaneous mutations.

Proteome oxidation elevates also UV-light induced mutagenesis and impairs cellular biosynthesis. In conclusion, protein

damage reduces the efficacy and precision of vital cellular processes resulting in high mutation rates and functional

degeneracy akin to cellular aging.
Author Summary

Cellular life is maintained by the activities of proteins that,

together, prevent molecular damage from occurring in the

first place and repair damaged DNA, proteins and other

damaged cellular components. Cellular fitness decreases

due to the fact that these proteins are themselves subject

to damage, leading to the progressive degeneracy of

cellular functions due to diminishing protein activity and

decreased precision. The ultimate liability to protein

function is the irreversible oxidative protein modification,

protein carbonylation. In our study, we have altered the

intrinsic susceptibility of proteins to oxidative damage via

alterations of translation fidelity and the accuracy of

protein folding. We have found that the increased quality

of proteome leads to an improved biosynthetic capacity of

cells, as well as to decreased mutation rates. Since cellular

aging can be defined as a progressive loss of nearly all vital

cellular functions and an increase in mutation rates, this

work suggests that oxidative proteome damage may be

the most likely cause of aging and age-related diseases.
Citation: Krisko A, Radman M (2013) Phenotypic and Genetic Consequences of Protein Damage.
 PLoS Genet 9(9): e1003810. doi:10.1371/journal.pgen.1003810
click to read the article

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Miroslav Radman - Molecular Biology and Genetics Scientist