Page 35 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Mitochondria and aging

the exact regulatory mechanisms of mitophagy and its Ethics approval and consent to participate
role in age-related diseases remain elusive. Over the past
decades, significant endeavors have been made to unravel Not applicable.
the role of mitochondria in aging, along with targeted Consent for publication
interventions. Yet, preventing mitochondrial dysfunction
in age-related disorders is a major challenge. Not applicable.
Nevertheless, NPs (NPs) are capable of targeting Availability of data
particular cells and localizing within mitochondria,
which facilitates treatments associated with age-related Not applicable.
diseases and mitochondrial dysfunction disorders. References
Hence, NPs conjugated with mitochondriotropic ligands
provide a promising tool for efficient mitochondrial 1. Flatt TJ. A new definition of aging? Front Genet. 2012;3:148.
delivery with proper nanoformulations. Although these doi: 10.3389/fgene.2012.00148
nanopreparations have been demonstrated to efficiently 2. Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging,
transport a wide range of payloads to the mitochondria and diseases. Clin Interv Aging. 2018:757-772.
in both in vivo and in vitro systems, various clinical and
pre-clinical investigations are needed to fully understand doi: 10.2147/cia.s158513
the safety of these drug delivery approaches. Recently, 3. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G.
therapeutic gene editing techniques to correct DNA The hallmarks of aging. Cell. 2013;153(6):1194-1217.
abnormalities, including mtDNA mutations and deletions, doi: 10.1016/j.cell.2013.05.039
have offered the promise of curing human age-related
diseases. Nevertheless, these techniques can help lower the 4. Petersen KF, Befroy D, Dufour S, et al. Mitochondrial
mutation rate within impaired mitochondria, leading to dysfunction in the elderly: Possible role in insulin resistance.
a shift in mtDNA heteroplasmy, reversing mitochondrial Science. 2003;300(5622):1140-1142.
defects, and hence improving mitochondrial function. doi: 10.1126/science.1082889
However, the mitochondrial bilayer membrane is a 5. Pagiatakis C, Musolino E, Gornati R, Bernardini G, Papait R.
significant obstacle to effective genetic manipulation. Epigenetics of aging and disease: A brief overview. Aging
Furthermore, most heteroplasmic mtDNA mutations differ Clin Exp Res. 2021;33:737-745.
from the wild-type by a single nucleotide, and the ability doi: 10.1007/s40520-019-01430-0
of gene editing tools to detect single-nucleotide mutations
is restricted, which can result in off-target editing or 6. Zhang S, Zhu N, Gu J, et al. Crosstalk between lipid rafts
catastrophic mtDNA loss. Besides, efficient tissue-specific and aging: New frontiers for delaying aging. Aging Dis.
in vivo delivery of therapeutic genes that mostly rely on 2022;13(4):1042.
AAV as the delivery vehicle has proven challenging. doi: 10.14336/ad.2022.0116
Finally, a better comprehension of the role of mitochondria 7. Roger AJ, Muñoz-Gómez SA, Kamikawa R. The
in aging remains a prerequisite for combating aging and origin and diversification of mitochondria. Curr Biol.
age-related disorders. 2017;27(21):R1177-R1192.

Acknowledgments doi: 10.1016/j.cub.2017.09.015
8. Cavalier-Smith T. Origin of mitochondria by intracellular
None.
enslavement of a photosynthetic purple bacterium. Proc Biol
Funding Sci. 2006;273(1596):1943-1952.
doi: 10.1098/rspb.2006.3531
None.
9. Brown WM, George M Jr., Wilson AC. Rapid evolution
Conflict of interest of animal mitochondrial DNA. Proc Natl Acad Sci U S A.
1979;76(4):1967-1971.
The authors declare they have no competing interests.
doi: 10.1073/pnas.76.4.1967
Author contributions 10. Lax NZ, Turnbull DM, Reeve AK. Mitochondrial mutations:
Conceptualization: All authors Newly discovered players in neuronal degeneration.
Writing – original draft: All authors Neuroscientist. 2011;17(6):645-658.
Writing – review & editing: All authors doi: 10.1177/1073858411385469

Volume 7 Issue 2 (2024) 13 doi: 10.36922/itps.1726