Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jan 14:5:455.
doi: 10.3389/fgene.2014.00455. eCollection 2014.

The aging clock and circadian control of metabolism and genome stability

Victoria P Belancio  1 , David E Blask  1 , Prescott Deininger  2 , Steven M Hill  1 , S Michal Jazwinski  3
Affiliations
Review

The aging clock and circadian control of metabolism and genome stability

Victoria P Belancio et al. Front Genet. .

Abstract

It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN) and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s) of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity, and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable, and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

Keywords: LINE-1; aging; light exposure at night; metabolism; retroelements.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Light exposure at night accelerates aging by impeding or enhancing processes associated with aging. (A) Usually aging involves normal light exposure that is characterized by alternating intervals of light and dark over a 24-h period, which result in circadian production of nocturnal melatonin. This leads to the synchronization of peripheral clock (PC) function controlling many biochemical processes in cells including L1 expression and activity (Deharo et al., 2014) and the DNA damage response (DDR). (B) Exposure to light at night (LAN) is reported to accelerate aging. LAN blocks nocturnal melatonin production which prevents synchronization of PCs, leading to the disruption of timely function of many biochemical processes in cells including L1 expression and activity, DDR, and metabolism.
FIGURE 2
FIGURE 2
Longitudinal effect of LAN on PC function, DDR, and metabolism. Schematic representation of the effect of normal light exposure versus LAN on the age-associated deterioration of PCs. The maintenance of the normal light/dark cycle promotes circadian melatonin output and synchronization of the PC (black line) with DDR and metabolic function (red line). An age-associated decline in melatonin production and melatonin receptor expression (Hill et al., 2010) leads to the gradual decline in the amplitude of the peripheral rhythms and potentially their synchronization with DDR and metabolic function. We hypothesize that LAN accelerates aging by promoting age-associated decline in the amplitude of the peripheral rhythms and their synchronization with DDR and metabolic function at early age. Individual genomes may provide molecular machinery to resist adverse effects of LAN, explaining the variation in lifespan observed in the human population.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anisimov V. N. (2003). The relationship between aging and carcinogenesis: a critical appraisal. Crit. Rev. Oncol. Hematol. 45 277–304 10.1016/S1040-8428(02)00121-X - DOI - PubMed
    1. Anisimov V. N., Baturin D. A., Popovich I. G., Zabezhinski M. A., Manton K. G., Semenchenko A. V., et al. (2004). Effect of exposure to light-at-night on life span and spontaneous carcinogenesis in female CBA mice. Int. J. Cancer 111 475–479 10.1002/ijc.20298 - DOI - PubMed
    1. Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F., et al. (2008). SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134 317–328 10.1016/j.cell.2008.06.050 - DOI - PubMed
    1. Baba K., Mazzoni F., Owino S., Contreras-Alcantara S., Strettoi E., Tosini G., et al. (2012). Age-related changes in the daily rhythm of photoreceptor functioning and circuitry in a melatonin-proficient mouse strain. PLoS ONE 7:e37799 10.1371/journal.pone.0037799 - DOI - PMC - PubMed
    1. Bass J. (2012). Circadian topology of metabolism. Nature 491 348–356 10.1038/nature11704 - DOI - PubMed

LinkOut - more resources