Editing Senescence (section)

==Genetic determinants of aging==
{{Main|Genetics of aging}}

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding [[yeast]] ''[[Saccharomyces cerevisiae]]'' to worms such as ''[[Caenorhabditis elegans]]'' and [[Drosophilidae|fruit flies]] (''[[Drosophila melanogaster]]''). Study of these organisms has revealed the presence of at least two conserved aging pathways.

Gene expression is imperfectly controlled, and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process as suggested by a study of such genes in yeast.<ref>{{cite journal | vauthors = Ryley J, Pereira-Smith OM | title = Microfluidics device for single cell gene expression analysis in Saccharomyces cerevisiae | journal = Yeast | volume = 23 | issue = 14–15 | pages = 1065–73 | year = 2006 | pmid = 17083143 | doi = 10.1002/yea.1412 | s2cid = 31356425 }}</ref> Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating the [[epigenetic]] factors play an important role in [[gene expression]] and aging as well as genetic factors. There is research into [[epigenetics of aging]].

The ability to repair DNA double-strand breaks declines with aging in mice<ref name="pmid25033455">{{cite journal |vauthors=Vaidya A, Mao Z, Tian X, Spencer B, Seluanov A, Gorbunova V |title=Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age |journal=PLOS Genet. |volume=10 |issue=7 |pages=e1004511 |date=July 2014 |pmid=25033455 |pmc=4102425 |doi=10.1371/journal.pgen.1004511 |doi-access=free }}</ref> and humans.<ref name="pmid27391797">{{cite journal |vauthors=Li Z, Zhang W, Chen Y, Guo W, Zhang J, Tang H, Xu Z, Zhang H, Tao Y, Wang F, Jiang Y, Sun FL, Mao Z |title=Impaired DNA double-strand break repair contributes to the age-associated rise of genomic instability in humans |doi-access=free |journal=Cell Death Differ. |volume=23 |issue=11 |pages=1765–77 |date=November 2016 |pmid=27391797 |pmc=5071568 |doi=10.1038/cdd.2016.65 }}</ref>

A set of rare hereditary ([[genetics]]) disorders, each called [[progeria]], has been known for some time. Sufferers exhibit symptoms resembling [[Accelerated aging disease|accelerated aging]], including [[wrinkle|wrinkled skin]]. The cause of [[Progeria|Hutchinson–Gilford progeria syndrome]] was reported in the journal ''[[Nature (journal)|Nature]]'' in May 2003.<ref>{{cite journal | vauthors = Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL | title = A progeroid syndrome in mice is caused by defects in A-type lamins | journal = Nature | volume = 423 | issue = 6937 | pages = 298–301 | date = May 2003 | pmid = 12748643 | doi = 10.1038/nature01631 | s2cid = 4360055 | bibcode = 2003Natur.423..298M | url = https://zenodo.org/record/1233263 |via=Zenodo |s2cid-access=free | access-date = 21 July 2021 | archive-date = 30 May 2022 | archive-url = https://web.archive.org/web/20220530212807/https://zenodo.org/record/1233263 | url-status = live }}</ref>
This report suggests that [[DNA damage]], not [[oxidative stress]], is the cause of this form of accelerated aging.

A study indicates that aging may shift activity toward short genes or shorter transcript length and that this can be countered by interventions.<ref>{{cite journal |last1=Stoeger |first1=Thomas |last2=Grant |first2=Rogan A. |last3=McQuattie-Pimentel |first3=Alexandra C. |last4=Anekalla |first4=Kishore R. |last5=Liu |first5=Sophia S. |last6=Tejedor-Navarro |first6=Heliodoro |last7=Singer |first7=Benjamin D. |last8=Abdala-Valencia |first8=Hiam |last9=Schwake |first9=Michael |last10=Tetreault |first10=Marie-Pier |last11=Perlman |first11=Harris |last12=Balch |first12=William E. |last13=Chandel |first13=Navdeep S. |last14=Ridge |first14=Karen M. |last15=Sznajder |first15=Jacob I. |last16=Morimoto |first16=Richard I. |last17=Misharin |first17=Alexander V. |last18=Budinger |first18=G. R. Scott |last19=Nunes Amaral |first19=Luis A. |title=Aging is associated with a systemic length-associated transcriptome imbalance |journal=Nature Aging |date=December 2022 |volume=2 |issue=12 |pages=1191–1206 |doi=10.1038/s43587-022-00317-6 |pmid=37118543 |pmc=10154227 |doi-access=free}}
* University press release: {{cite news |title=Aging is driven by unbalanced genes, finds AI analysis of multiple species |url=https://phys.org/news/2022-12-aging-driven-unbalanced-genes-ai.html |access-date=18 January 2023 |work=[[Northwestern University]] |via=phys.org |date=December 9, 2022 |archive-date=2 February 2023 |archive-url=https://web.archive.org/web/20230202173100/https://phys.org/news/2022-12-aging-driven-unbalanced-genes-ai.html |url-status=live }}
* News article about the study: {{cite news |last1=Kwon |first1=Diana |title=Aging Is Linked to More Activity in Short Genes Than in Long Genes |url=https://www.scientificamerican.com/article/aging-is-linked-to-more-activity-in-short-genes-than-in-long-genes/ |url-access=subscription |date=January 6, 2023 |access-date=18 January 2023 |work=Scientific American |archive-date=17 January 2023 |archive-url=https://web.archive.org/web/20230117052143/https://www.scientificamerican.com/article/aging-is-linked-to-more-activity-in-short-genes-than-in-long-genes/ |url-status=live }}</ref>