Theories of biological aging: Genes, proteins, and free radicals

Abstract

Traditional categorization of theories of aging into programmed and stochastic ones is outdated and obsolete. Biological aging is considered to occur mainly during the period of survival beyond the natural or essential lifespan (ELS) in Darwinian terms. Organisms survive to achieve ELS by virtue of genetically determined longevity assuring maintenance and repair systems (MRS). Aging at the molecular level is characterized by the progressive accumulation of molecular damage caused by environmental and metabolically generated free radicals, by spontaneous errors in biochemical reactions, and by nutritional components. Damages in the MRS and other pathways lead to age-related failure of MRS, molecular heterogeneity, cellular dysfunctioning, reduced stress tolerance, diseases and ultimate death. A unified theory of biological aging in terms of failure of homeodynamics comprising of MRS, and involving genes, milieu and chance, is acquiring a definitive shape and wider acceptance. Such a theory also establishes the basis for testing and developing effective means of intervention, prevention and modulation of aging.

High glucose induces adipogenic differentiation of muscle-derived stem cells

“…Various mechanisms appear to synergize in increasing ROS production, ranging from the activity of mitochondrial respiratory complexes to the activation of enzymatic systems, such as NOX isoforms, NO synthase, and xanthine oxidase (22). Despite the presence of scavenging systems (e.g., superoxide dismutase and catalase), the damaging effects of ROS have been proposed to be responsible for progressive organ degeneration (23). However, the role of ROS is not only restricted to cell damage induction.…”

When a theory of aging ages badly

“…Discrimination between the core statement and the associated hypotheses of a theory is crucial because a theory could survive with some erroneous hypotheses but should not survive with an inaccurate core statement. Strangely, even if aging has been suggested to be a multi-causal process linked to a variety of molecular and cellular sources of damage [3][4][5][6], almost all popular theories of aging actually revolve around postulating a single physiological cause of aging. Of course, if aging is in fact multi-factorial and does not have a single cause then each of the theories that postulate a single cause might have some degree of truth.…”

Âge et stress oxydant

“…D'autres mécanismes pourraient également être à l'origine du vieillissement : anomalies ou mutations géné-tiques, modifications des protéines, perte de fonction immunitaire, inflammation des tissus, augmentation de l'incidence des tumeurs [3]. Enfin, il est probable que le vieillissement ne soit pas génétiquement programmé par des « gérontogènes 1 » [11].…”

“…Selon Bokov et al [2], pour que la théorie d'une responsabilité des radicaux libres dans le vieillissement soit validée, trois critères doivent être respectés : (1) les dommages moléculaires causés par le stress oxydant doivent s'accumuler avec l'âge ; (2) les manipulations diététiques, pharmacologiques ou génétiques augmentant la longévité doivent en parallèle diminuer les dommages moléculaires ; (3) les manipulations diminuant le niveau de stress oxydant doivent en parallèle allonger la durée de vie. De nombreuses études ont confirmé le premier critère [11]. De même, l'augmentation de la longévité par restriction calorique chez la souris [12] ou par manipulation généti-que chez un invertébré [2] réduit les dommages moléculaires associés au stress oxydant.…”