Human chromosomes (and most eukaryotes) contain Linear DNA at the ends of which are telomeres which are long repititive DNA sequences. In linear chromosomes, DNA polymerase cannot fully replicate chromosome ends, leading to progressive shortening with each cell division. Telomeres help prevent loss of useful information during DNA replication and, in turn, are shortened with each cell division.
Hayflick Limit and Replicative Ageing
The shortening of telomeres is termed Telomere Attrition, and this is one of the 13 hallmarks of ageing (biological ageing at the cellular level). The maximum number of times a cell can replicate before cell division stops (due to the telomere region being exhausted) is known as the Hayflick limit (typically 40-60 times for a normal human somatic cell). Methods to increase this limit should positively impact this Ageing Hallmark, while ensuring that excessive telomere length does not lead to unwanted effects (long telomeres are often observed in multiple types of cancer cells).
Circular DNA without telomeres performing rolling-circle replication[1]
In this individual project (to be formally proposed in the ongoing HTGAA 2026 cohort), I mainly dwell upon two potential approaches that could help remove this nature-imposed cellular replication limit (discovered by Leonard Hayflick) thereby increasing organismal lifespan; the other bottlenecks of lifespan or how whether this will have impact of healthspan are considered out of scope for this project ideation (although I wish to perform experiments on single and multi-cellular organisms regarding the after effects of such synthetic tweaks which could also provide some understanding on the effects on cellular/tissue healthspans).
References
Sakatani, Y., Yomo, T. & Ichihashi, N., Self-replication of circular DNA by a self-encoded DNA polymerase through rolling-circle replication and recombination.,
Scientific Reports, 2018.
https://www.nature.com/articles/s41598-018-31585-1
About me
Born in Kolkata, India, I have spent around two-thirds of my life in my hometown (also known as the City of Joy)
Zealous to strategize on colonizing planets in our Solar System (favourite: Saturn) with a multi-pronged approach of surviving the Solar Supernovae (1. Moving away from the Sun in search of other stars, as well as 2. Developing heat-resistant materials and organisms to survive the Solar Supernovae event by shifting Earth)
I like playing Chess and Football, and solving Problems…
Power Engineer (renewable energy systems); Operational Researcher (mathematical modelling and heuristic design for large scale optimization)
