Exploring Recent Advances- A Review of Key Topics in Biology from Leading Journals- Mitochondria and Aging

Exploring Recent Advances- A Review of Key Topics in Biology from Leading Journals- Mitochondria and Aging

Mitochondria have traditionally been considered to mainly function in the production of ATP through oxidative phosphorylation (OXPHOS). However, they are recently appreciated for their participation in age-related pathways such as reactive oxygen species (ROS). Additionally, they are unique organelles as they possess their own genome, which is a circular DNA called mitochondrial DNA (mtDNA). Aging can be described as the progressive decline in organism functions, possibly caused by the progressive failure of multiple factors of cell functioning. In mouse models, premature aging is observed due to an increase in somatic mtDNA levels caused by genetic defects. This proves that there is observational and experimental evidence that mammalian aging is closely associated with mitochondrial dysfunction.

Somatic mtDNA Mutations and Aging

Prominent mtDNA mutations are deletions and point mutations. Both have been shown to accumulate with age in human tissues such as skeletal muscles, brain, and heart. Many reports have associated the aging of human skin with somatic mutations in mtDNA, as these mutations are seen to increase in skin regions that have been exposed to UV radiation (Larsson, 2010). These mutations also implicate aging phenotypes. For instance, after approximately 25 weeks, the normal-appearing mtDNA mutator mice begin to portray several progressive premature aging symptoms, including impaired hearing, loss of hair and gray hair, enlarged heart, reduced lifespan, and reduced fertility. This is due to the accumulation of high amounts of mutations, owing to the fact that they have a homozygous knock-in mutation that causes proofreading deficiency.

Additionally, patients with HIV exhibit symptoms of premature aging, including early onset of frailty and premature degenerative cardiovascular diseases associated with age. It has been documented that certain anti-retroviral drugs can inhibit mtDNA polymerase, and patients administered these drugs show clonal expansion of mitochondrial mutations and OXPHOS dysfunction (Kauppila, Kauppila, and Larsson, 2017).

Effects of mtDNA Mutations Clonal Expansions

Clonal expansion of somatic mtDNA mutations leads to mosaic respiratory chain deficiency in different organs during mammalian aging. In most publications, large deletions in the mtDNA that are single are clonally expanded. Moreover, the accumulation of point mutations accumulate in stem cells causes complex IV (COX) deficiency. With age, COX-deficient progenitors increase, suggesting that clonal expansions of mtDNA point mutations contribute to the aging process in stem cells. In human aging, patterns of clonal expansions in mtDNA mutations that cause COX deficiency are observed in colonic crypts. These patterns are similar to those observed in aging heterozygous mtDNA mutator mice undergoing a moderate increase of mutations.

Additionally, mtDNA mutator mice between the ages of 3 to 7 months expressing point mutation accumulation in the small intestine express OXPHOS dysfunction, and changes in their morphology are seen in aging mice and humans. The failure of organoids derived from the small intestines of the mtDNA mutator mice indicates the existence of epithelial stem cell dysfunctions.

Reactive Oxygen Species (ROS) Signaling

Though mtDNA mutation is not the major cause of mitochondrial ROS, ROS is a toxic byproduct of metabolism that participates in the aging process as it causes detrimental damage to various cell components. Also, ROS signaling molecules play a role in regulating health span and/or lifespan in organisms as they are normal physiological processes. As such, the lifespan of several model organisms like worms, flies, and mice has been extended by the use of retrograde ROS. In worms with an impairment of insulin/IGF-1 signaling, lifespan extension is mediated by retrograde ROS signaling. Also, such longevity can be reduced by approximately 60% by inhibiting ROS signals using antioxidants. In addition, ROS can lead to epigenetic alterations. For instance, in yeast, the binding capacity of chromatin of histone demethylase Rph1p can be regulated by ROS, thus extending their chronological lifespan (Son and Lee, 2019).

In summary, somatic mutations in the mitochondrial DNA, the clonal expansion of these mutations, and dysfunctions in mitochondrial age-related pathways, such as the ROS signaling pathway, contribute to the aging process in mammals. Furthermore, the biology of mitochondrial communication with the endoplasmic reticulum, peroxisomes, and lysosomes is a new prospect in mitochondria’s contribution to aging. Disruption of this three-communication triangle is closely associated with aging and diseases associated with age. However, the mechanisms of mitochondrial communication are poorly understood, leaving room for further scientific research.

References

Kauppila, T. E. S., Kauppila, J. H. K., and Larsson, N. -G. (2017). Mammalian Mitochondria and Aging: An Update. Cell Metabolism, 25(1), pp.57-71.

Larsson, N. –G. (2010). Somatic Mitochondrial DNA Mutations in Mammalian Aging. Annual Review of Biochemistry, 79(1), pp.683-706.

Son, J. M., and Lee, C. (2019). Mitochondria: multifaceted regulators of aging. BMB Reports, 52(1), pp.13-23.

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Go Through the UM library page and use Scopus, Web of Science, or any journal article database of your choice to find a review article published in a good review journal on a topic in biology that you find interesting. Alternatively, you can go to a review journal’s website (e.g. Trends in Cell Biology, Nature, Science, so on) and just browse. The review article can be based upon what we’ve covered in the lecture so far, and I will encourage doing this or something else that you dig or find important.

If you have any questions regarding your topic or review article, send me an email. ii. Using the database, find two newer primary journal articles that reference your review article. iii. Write a short paper on what you’ve found. Describe what was generally discussed in the review article, and then state how the experiments outlined in the two primary articles helped expand our knowledge on the subject area. Good things to include are what hypotheses the primary articles were testing, how they tested them, and a summary of how the new knowledge fits into what we previously knew (i.e., in the context of the material presented in the review article). Cite and reference the review article and the two primary articles properly (details below)
On top of the title of your paper, include your name and your student number. The text section of the paper is to be two pages, double-spaced.
Next page: References (single-spaced), in APA style
Assignment format and references
Use either Calibri 11 point or Ariel 11 point as a font. Use the ‘normal’ margin settings in Word (2.54 cm on each margin). You are going to use the APA style of citation, it comes across easily in sciences, be consistent.