Abstract
In aging cells, genomic instability is now recognized as a hallmark event. Throughout life, cells encounter multiple endogenous and exogenous DNA damaging events that are mostly repaired, but inevitably DNA mutations, chromosome rearrangements, and epigenetic deregulation begins to mount. Now that people are living longer, more and more late life time is spent suffering from age-related disease, in which genomic instability plays a critical role. However, several major questions remain heavily debated, such as the following: When does aging start? How long can we live? In order to minimize the impact of genomic instability on longevity, it is important to understand when aging starts, and to ensure repair mechanisms remain optimal from the very start to the very end. In this review, the interplay between the stress and nutrient response networks, and the regulation of homeostasis and genomic stability, is discussed. Mechanisms that link these two networks are predicted to be key lifespan determinants. The Anaphase Promoting Complex (APC), a large evolutionarily conserved ubiquitin ligase, can potentially serve this need. Recent work demonstrates that the APC maintains genomic stability, mounts a stress response, and increases longevity in yeast. Furthermore, inhibition of APC activity by glucose and nutrient response factors indicates a tight link between the APC and the stress/nutrient response networks.
Highlights
When does the aging process begin? How long can we live? Why do we age? These questions are highly debated with no distinct, definitive answers
The novel concept that activation of a cell cycle regulator, the Anaphase Promoting Complex, which is required for maintenance of cell health, inhibition of cancer progression, and enhanced longevity, will be explored
If targeted degradation of Gcn5 by the Anaphase Promoting Complex (APC) is conserved from yeast to humans, this may be critical for tumor suppression and maintenance of genomic stability, as increased H3K9Ac is associated with DNA damage, genomic instability, and progression of multiple myeloma [122]
Summary
When does the aging process begin? How long can we live? Why do we age? These questions are highly debated with no distinct, definitive answers. Hayflick eventually concluded that aging is a stochastic program that begins after reproductive maturity in animals, resulting in the loss of molecular fidelity. This loss of fidelity surpasses repair capacity, leaving individuals prone to age-related diseases [8,9]. The stochastic idea of aging gained traction when the free radical theory of aging was proposed. This theory states that aging occurs due to the natural wear and tear of cellular machinery and biological substances due to exposure to free radicals generated within the cell [12]. The novel concept that activation of a cell cycle regulator, the Anaphase Promoting Complex, which is required for maintenance of cell health, inhibition of cancer progression, and enhanced longevity, will be explored
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
