Is natural aging the result of telomeres shortening, or is it not that simple?

[Trekkie_DFW]

I was looking up why dogs don't live as long as humans, and I found a lot of very sophisticated-sounding answers about things like metabolism and the trade off between maturing and reproducing more quickly vs taking longer to develop but having a longer lifespan (the whole--live fast, die young thing), and that makes sense, but...

I saw something on a show..a Korean rom com, of all things...about telomere length and aging, and after researching it, I want to know--isn't that the real cause of aging? Aren't the explainations we often hear about reproduction and metabolism missing the real reason why species have different lifespans? Or is that too simple (or inaccurate) an explanation? 

 

Thanks. 

[Endy0816]

Recently been found that the rate that they shorten seems to play the larger role.

Quote

Although previous studies suggest that telomeres are involved in aging, no correlation has been found between the lifespan of a species and initial telomere length. Humans for example have shorter telomeres than mice (5–15 kb versus 50 kb) but have much longer lifespans.

A new study used high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) to measure at different ages telomere length in peripheral blood mononuclear cells from individuals of different species of birds and mammals (including mouse, goat, American flamingo, and Sumatran elephant), and calculate telomere shortening rate for each species. The results show that telomere shortening rate, but not initial telomere length, is a powerful predictor of species lifespan.

https://www.nature.com/articles/s41684-019-0388-5#:~:text=Although previous studies suggest that,but have much longer lifespans.

 

Complicating things is the fact that telomeres can be lengthened as well via telomerase.

Further complicating things is that only us Eukaryotes have this issue.

[CharonY]

Other factors, including mitochondrial degradation related to oxidative stress are also commonly associated wit aging, as well as chronic inflammatory responses (both might be at least partially related to the role of diet in longevity). Further factors include mutations and associated dysregulation, proteomic changes especially related to protein turnover and so on. There are many levels to look at the issue, starting from the cellular, to tissue to organs and organismal levels. As such there are many proposals from different specializations and generally speaking it has become clear that many factors are involved, thought he causal connections and mechanisms are not necessarily clear (e.g. do we see protein damage due to e.g. due to mutations are do those damages impact our ability to repair DNA damages? Or do they cause oxidative damages which in turn cause DNA damage?). 

While I am not expert in that field I also do not think that we have a clear understanding of the relevance of these elements and which one would be more relevant than the other. Often, it depends on the precise research question. 

[Doctor Derp]

On 7/11/2022 at 4:25 PM, Trekkie_DFW said:

 

I saw something on a show..a Korean rom com, of all things...about telomere length and aging, and after researching it, I want to know--isn't that the real cause of aging?

 

AFAIK telomeres are caps which protect the integrity of DNA data. 

Damage to telomeres can be accelerated by exposure to pollution, radiation, sunlight, toxins, etc. 

As telomere protection is worn away. Genetic data in DNA becomes more susceptible to damage and corruption. Causing cell replication to become more inaccurate and abnormal.

Its not actually the telomeres shortening that affects aging. But their shortening does provide a reduction to their protection of genetic info.

[CharonY]

6 minutes ago, Doctor Derp said:

AFAIK telomeres are caps which protect the integrity of DNA data. 

Not quite true. Telomeres are actually genetic material themselves and as such have no protective properties over other stretches of DNA. Essentially, they are repetitive sequences of DNA at the ends of chromosomes. They shorten during replication, though reactive oxygen species are also thought to play a role in telomere shortening. 

[Doctor Derp]

49 minutes ago, CharonY said:

Telomeres have no protective properties over other stretches of DNA. 

 

The above claim can be disproven by a quick google search.

 

Quote

Located at the tips of each of our 46 chromosomes, telomeres help protect DNA and are particularly important during cell division. Telomeres have received a lot of notoriety due to their relationship with aging. These protective structures shorten with each cell division, exposing DNA to potential danger. In time, telomeres get too short to shield DNA. That’s when cells stop working, function poorly or, even worse, develop disease.

https://www.faim.org/telomeres-increase-longevity-by-protecting-your-dna

 

[CharonY]

On 10/1/2022 at 5:41 PM, Doctor Derp said:

 

The above claim can be disproven by a quick google search.

 

 

It is not working the way you think. The issue here is not exposure of DNA to external factors, they will have that all the time, anyway as active regions have to be unwound (most of the time far from the ends where the telomeres sit). Rather, they are involved in solving the end of replication issue (which is not the subject here) but also interacting with our own damage response system. The issue is really is focused on the end of chromosomes. If we have DNA damage, our response pathways either try to fix it or it can lead to further degradation pathways, which ultimately can result in cell arrest or death. To prevent that, telomeres together with a protein complex called shelterin. There are different functions involved, but ultimately they stop a number of different pathways that are involved in DNA repair pathways (specifically nonhomologous end joining and homology directed repair, in case you want to read up) as well as signaling pathways that are activated when DNA breaks are detected (ATR and ATM).

So in short, the resulting structures are not so much about exogenous damage protection, but really about protecting our ends from our repair systems. 

Edit: I found an article on wiki that explains it a bit: https://en.wikipedia.org/wiki/Shelterin

 

 

[iNow]

Shelterin. Sounds like folks response to a tornado in Kentucky. 

[Endy0816]

22 hours ago, CharonY said:

It is not working the way you think. The issue here is not exposure of DNA to external factors, they will have that all the time, anyway as active regions have to be unwound (most of the time far from the ends where the telomeres sit). Rather, they are involved in solving the end of replication issue (which is not the subject here) but also interacting with our own damage response system. The issue is really is focused on the end of chromosomes. If we have DNA damage, our response pathways either try to fix it or it can lead to further degradation pathways, which ultimately can result in cell arrest or death. To prevent that, telomeres together with a protein complex called sheltering. There are different functions involved, but ultimately they stop a number of different pathways that are involved in DNA repair pathways (specifically nonhomologous end joining and homology directed repair, in case you want to read up) as well as signaling pathways that are activated when DNA breaks are detected (ATR and ATM).

So in short, the resulting structures are not so much about exogenous damage protection, but really about protecting our ends from our repair systems. 

Edit: I found an article on wiki that explains it a bit: https://en.wikipedia.org/wiki/Shelterin

 

 

The shift from circular to linear DNA must have involved some really unique circumstances.

[iNow]

On 10/1/2022 at 8:18 PM, CharonY said:

Edit: I found an article on wiki that explains it a bit: https://en.wikipedia.org/wiki/Shelterin

Thanks for this link, btw. It seems our bodies do the same thing with our telomeres that I do when I cut a cord which is later likely to fray: I seal it or coat it with wax or somehow melt the threads together to prevent further deterioration. 

Edited October 4, 2022 by iNow

[CharonY]

On 10/2/2022 at 6:21 PM, Endy0816 said:

The shift from circular to linear DNA must have involved some really unique circumstances.

It certainly created some challenges. Interestingly, in eukaryotes linearization is thought to be a essential for meiosis to happen. However, there are a couple of prokaryotes with linear chromosomes. While they have also have to deal with end of replication issues, (and some e.g. overcome it by transiently circularizing the linear chromosomes during replication) it is much less clear why they have them. Or at least I did not come across strong hypothesis what that advantage could be (as circularity is clearly maintained otherwise in prokaryotes).