Longevity Wiki - User contributions [en-GB]

Telomeres

2021-12-21T16:56:27Z

LM:

Telomeres (from the Greek "''telos''", meaning "end", and "''meros''", meaning "part") are protective caps on the ends of chromosomes. Like the rest of the chromosome, they are made up of DNA, but this DNA does not code for any proteins.

Telomeres are made up of a short, repeated sequence of DNA bases. (In humans the sequence is TTAGGG.)
[[File:Chromosomes, with the telomeres shown in pink.png|thumb|Chromosomes with the telomeres shown in pink. Image by AJC1 - <nowiki>https://theconversation.com/end-of-ageing-and-cancer-scientists-unveil-structure-of-the-immortality-enzyme-telomerase-95591</nowiki>, CC BY-SA 4.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=71691237</nowiki>]]
The purpose of telomeres is to protect the rest of the chromosome from damage, particularly during cell division. Every time a cell divides, the chromosome is shortened a bit (see "end replication problem" below), and the sacrificed DNA comes from the telomeres rather than from the DNA that codes for proteins.

== Telomere loss with cell division (the "end replication problem") ==
When a cell divides, the DNA strands that make up the chromosomes also divide, and a complementary strand is synthesised for each half, resulting in two copies of the original chromosome. However, the ends of the chromosomes - 25-200 DNA bases - cannot be replicated. This is known as the "end replication problem". The process is explained in more detail below.

==== DNA replication during cell division ====
During cell division the paired DNA strands separate in an “unzipping” motion. Each DNA strand has what is known as a 5’ end and a 3’ end (dictated by the orientation of the component molecules). The DNA strands in each pair run in opposite directions from each other.

Enzymes move along the separating strands from the open end to the closed end, synthesizing a complementary DNA strand for each of the two strands as they go.
[[File:DNA replication.jpg|center|frame|DNA replication. Image by Genomics Education Programme - DNA replication, CC BY 2.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=50542885</nowiki>]]

This synthesis process begins when a section of RNA, known as a "primer", attaches to the parent strand, providing a molecule onto which the newly synthesized DNA can be attached. (The RNA primers are later removed and replaced with DNA.)

However, the DNA-synthesizing enzymes can only add DNA in one direction - from the 3' end of the parent strand to the 5' end. On one of the strands (the "leading strand") the enzymes are moving in this direction along the parent strand, so this is not a problem. However, on the other strand (the "lagging strand"), which is oriented in the opposite direction, the enzymes are moving in the wrong direction to be able to lay down DNA.

This problem is solved by laying down DNA in a series of “backstitches” (known as “Okazaki fragments”). Each backstitch is started off by an RNA primer attached to the parent strand. The primers are later replaced with DNA, which is also laid down as backstitches.

However, the final primer, at the end of the lagging strand, cannot be replaced with DNA because there is nothing to attach this final backstitch to. This is known as the "end replication problem".

The end replication problem means that the new DNA strand is shorter than the parent strand.

In order to ensure that this shortening does not result in the loss of important bases, a string of disposable bases is provided at the end of the strand. This string of disposable bases is called a telomere and consists of a short sequence (TTAGGG in humans) repeated multiple times.

The process of sacrificing these bases is called “telomere attrition”.

This attrition eventually results in telomeres that are too short to allow the cell to divide any further. This state is known as "replicative senescence" and it triggers programmed cell death.

However, if telomeres are maintained (see "How can telomeres be maintained?" below), the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

Telomeres

2021-12-21T16:46:08Z

LM:

Telomeres (from the Greek "''telos''", meaning "end", and "''meros''", meaning "part") are protective caps on the ends of chromosomes. Like the rest of the chromosome, they are made up of DNA, but this DNA does not code for any proteins.

Telomeres are made up of a short, repeated sequence of DNA bases. (In humans the sequence is TTAGGG.)
[[File:Chromosomes, with the telomeres shown in pink.png|thumb|Chromosomes with the telomeres shown in pink. Image by AJC1 - <nowiki>https://theconversation.com/end-of-ageing-and-cancer-scientists-unveil-structure-of-the-immortality-enzyme-telomerase-95591</nowiki>, CC BY-SA 4.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=71691237</nowiki>]]
The purpose of telomeres is to protect the rest of the chromosome from damage, particularly during cell division. Every time a cell divides, the chromosome is shortened a bit (see "end replication problem" below), and the sacrificed DNA comes from the telomeres rather than from the DNA that codes for proteins.

== Telomere loss with cell division (the "end replication problem") ==
When a cell divides, the DNA strands that make up the chromosomes also divide, and a complementary strand is synthesised for each half, resulting in two copies of the original chromosome. However, the ends of the chromosomes - 25-200 DNA bases - cannot be replicated. This is known as the "end replication problem". The process is explained in more detail below.

==== DNA replication during cell division ====
During cell division the paired DNA strands separate in an “unzipping” motion. Each DNA strand has what is known as a 5’ end and a 3’ end (dictated by the orientation of the component molecules). The DNA strands in each pair run in opposite directions from each other.

Enzymes move along the separating strands from the open end to the closed end, synthesizing a complementary DNA strand for each of the two strands as they go.
[[File:DNA replication.jpg|center|frame|DNA replication. Image by Genomics Education Programme - DNA replication, CC BY 2.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=50542885</nowiki>]]

This synthesis process begins when a section of RNA, known as a "primer", attaches to the parent strand, providing a molecule onto which the newly synthesized DNA can be attached. (The RNA primers are later removed and replaced with DNA.)

However, the DNA-synthesizing enzymes can only add DNA in one direction along the parent strand. This is not a problem on the leading strand, where DNA is laid down continuously as the enzymes move along it. However, on the lagging strand, the enzymes are moving in the wrong direction to be able to lay down DNA.

This problem is solved by laying down DNA in a series of “backstitches” (known as “Okazaki fragments”). Each backstitch is started off by an RNA primer attached to the parent strand. The primers are later replaced with DNA, which is also laid down as backstitches.

However, the final primer, at the end of the lagging strand, cannot be replaced with DNA because there is nothing to attach this final backstitch to. This is known as the "end replication problem".

The end replication problem means that the new DNA strand is shorter than the parent strand.

In order to ensure that this shortening does not result in the loss of important bases, a string of disposable bases is provided at the end of the strand. This string of disposable bases is called a telomere and consists of a short sequence (TTAGGG in humans) repeated multiple times.

The process of sacrificing these bases is called “telomere attrition”.

This attrition eventually results in telomeres that are too short to allow the cell to divide any further. This state is known as "replicative senescence" and it triggers programmed cell death.

However, if telomeres are maintained (see below), the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

File:DNA replication.jpg

2021-12-21T16:25:55Z

LM:

DNA replication.
Image by Genomics Education Programme - DNA replication, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=50542885

Telomeres

2021-11-04T21:15:37Z

LM: Adjusted and added to introduction.

Telomeres (from the Greek "''telos''", meaning "end", and "''meros''", meaning "part") are protective caps on the ends of chromosomes. Like the rest of the chromosome, they are made up of DNA, but this DNA does not code for any proteins.

Telomeres are made up of a short, repeated sequence of DNA bases. (In humans the sequence is TTAGGG.)

The purpose of telomeres is to protect the rest of the chromosome from damage, particularly during cell division. Every time a cell divides, the chromosome is shortened a bit (see "end replication problem"), and the sacrificed DNA comes from the telomeres rather that from the DNA that codes for proteins.

== Telomere loss with cell division (the "end replication problem") ==
When a cell divides, the DNA strands that make up the chromosomes also divide, and a complementary strand is synthesised for each half, resulting in two copies of the original chromosome. However, the ends of the chromosomes - 25-200 DNA bases - cannot be replicated. This is known as the "end replication problem". The process is explained in more detail below.

==== DNA replication during cell division ====
During cell division the paired DNA strands separate in an “unzipping” motion. Enzymes move along the strands from the open end to the closed end, synthesizing a complementary DNA strand for each of the two strands as they go.

This synthesis process begins when a section of RNA, known as a "primer", attaches to the parent strand. The primer provides a 3’ hydroxyl group, onto which the newly synthesized DNA can be attached. The RNA primers are later removed and replaced with DNA.

DNA strands have a 5’ molecule at one end and a 3’ molecule at the other, and the paired DNA strands - the “leading strand” and the “lagging strand” - run in opposite directions from each other.

As the DNA-synthesizing enzymes run along the unzipping strand, they will therefore be moving towards the 5’ end of one strand and the 3’ end of the other.

However, DNA can only be added from the 5’ end to the 3’ end. This means that for the strand on which the enzymes are moving in the “wrong” direction, DNA cannot be added continuously; instead, it has to be added in a series of “backstitches”, each started off with an RNA primer, which is later replaced with DNA.

The final primer, at the end of the lagging strand, cannot be replaced with DNA because there isn’t a 3’ hydroxyl group beyond the end of the strand to start it off. Once this final primer is removed, some bases are therefore left unreplicated, making the new DNA strand shorter than the parent strand. This is known as the "end replication problem".

In order to avoid losing important bases during this shortening, the DNA contains a string of disposable bases at the end of the strand. This string of disposable bases is called a telomere and consists of a short sequence (TTAGGG in humans) repeated multiple times.

The process of sacrificing these bases is called “telomere attrition”.

This attrition eventually results in telomeres that are too short to allow the cell to divide any further. This state is known as "replicative senescence" and it triggers programmed cell death.

However, if telomeres are maintained, the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

File:Chromosomes, with the telomeres shown in pink.png

2021-11-04T15:18:36Z

LM:

Chromosomes, with the telomeres shown in pink

Telomeres

2021-10-03T22:01:06Z

LM:

Telomeres are short, repetitive sections of DNA bases at the tips of the chromosomes. In humans the repeated sequence is TTAGGG.

== Telomere loss with cell division (the "end replication problem") ==
Every time a cell divides, it loses 25-200 DNA bases because of the “end replication problem”.

During cell division the paired DNA strands separate in an “unzipping” motion. Enzymes move along the strands towards the “zipped” end, synthesizing a complementary strand for each one as they go.

This DNA synthesis needs to be started off with a 3’ hydroxyl group, which is provided by an RNA “primer” that attaches to the parent strand. These RNA primers are later removed and replaced with DNA.

DNA strands have a 5’ molecule at one end and a 3’ molecule at the other, and the paired DNA strands - the “leading strand” and the “lagging strand” - run in opposite directions from each other.

As the DNA-synthesizing enzymes run along the unzipping strand, they will therefore be moving towards the 5’ end of one strand and the 3’ end of the other.

However, DNA can only be added from the 5’ end to the 3’ end. This means that for the strand on which the enzymes are moving in the “wrong” direction, DNA cannot be added continuously; instead, it has to be added in a series of “backstitches”, each started off with an RNA primer, which is later replaced with DNA.

The final primer, at the end of the lagging strand, cannot be replaced with DNA because there isn’t a 3’ hydroxyl group beyond the end of the strand to start it off. Once this final primer is removed, some bases are therefore left unreplicated, making the new DNA strand shorter than the parent strand. This is known as the "end replication problem".

In order to avoid losing important bases during this shortening, the DNA contains a string of disposable bases at the end of the strand. This string of disposable bases is called a telomere and consists of a short sequence (TTAGGG in humans) repeated multiple times.

The process of sacrificing these bases is called “telomere attrition”.

This attrition eventually results in telomeres that are too short to allow the cell to divide any further, which triggers programmed cell death.

However, if telomeres are maintained, the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

Telomeres

2021-10-03T21:59:28Z

LM: Expanded section /* Telomere loss with cell division */

Telomeres are short, repetitive sections of DNA bases at the tips of the chromosomes. In humans the repeated sequence is TTAGGG.

== Telomere loss with cell division (the "end replication problem") ==
Every time a cell divides, it loses 25-200 DNA bases because of the “end replication problem”.

During cell division the paired DNA strands separate, in an “unzipping” motion. Enzymes move along the strands towards the “zipped” end, synthesizing a complementary strand for each one as they go.

This DNA synthesis needs to be started off with a 3’ hydroxyl group, which is provided by an RNA “primer” that attaches to the parent strand. These RNA primers are later removed and replaced with DNA.

DNA strands have a 5’ molecule at one end and a 3’ molecule at the other, and the paired DNA strands - the “leading strand” and the “lagging strand” - run in opposite directions from each other.

As the DNA-synthesizing enzymes run along the unzipping strand, they will therefore be moving towards the 5’ end of one strand and the 3’ end of the other.

However, DNA can only be added from the 5’ end to the 3’ end. This means that for the strand on which the enzymes are moving in the “wrong” direction, DNA cannot be added continuously; instead, it has to be added in a series of “backstitches”, each started off with an RNA primer, which is later replaced with DNA.

The final primer, at the end of the DNA strand, cannot be replaced with DNA because there isn’t a 3’ hydroxyl group beyond the end of the strand to start it off. Once this final primer is removed, some bases are therefore left unreplicated, making the new DNA strand shorter than the parent strand. This is known as the "end replication problem".

In order to avoid losing important bases during this shortening, the DNA contains a string of disposable bases at the end of the strand. This string of disposable bases is called a telomere and consists of a short sequence (TTAGGG in humans) repeated multiple times.

The process of sacrificing these bases is called “telomere attrition”.

This attrition eventually results in telomeres that are too short to allow the cell to divide any further, which triggers programmed cell death.

However, if telomeres are maintained, the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

Telomeres

2021-08-29T19:36:22Z

LM: Created new article: definition of telomeres, telomere loss, telomere maintenance.

Telomeres are short, repetitive sections of DNA bases at the tips of the chromosomes. In humans the repeated sequence is TTAGGG.

== Telomere loss with cell division ==
Every time a cell divides, it loses 25-200 DNA bases. The DNA that is “sacrificed” for this purpose comes from the telomeres. (This process is called “telomere attrition”.)

This attrition eventually results in telomeres that are too short to allow the cell to divide any further, which triggers programmed cell death<ref>https://www.yourgenome.org/facts/what-is-a-telomere</ref>.

However, if telomeres are maintained, the cell can continue to divide indefinitely.

=== How can telomeres be maintained? ===
Telomeres are made and maintained by the enzyme telomerase, which adds the telomere DNA sequence to the ends of the chromosomes.

Telomerase is present only in small concentrations in somatic cells (the body's non-reproductive cells) and is not regularly used by them. However, it is present in high concentrations in germline cells (eggs and sperm), stem cells and cancer cells, and it serves to maintain the telomeres when these cells divide. This means these cells do not age and can continue dividing indefinitely.

Negligible senescence

2021-08-12T21:45:16Z

LM:

== Definition ==
Negligible senescence refers to an absence of gradual deterioration with age, specifically an absence of:

# age-related increases in disease incidence and associated death rate;
# decrease in reproductive capability; and
# deterioration in physiological capacity, such as strength, mobility and sensory acuity.

It should be noted that negligible senescence is not synonymous with immortality. An organism that displays negligible senescence - i.e. no gradual deterioration - can still die of a sudden process, whether internal or external, such as predator attack, accident, starvation, exposure to adverse environmental conditions, disease or semelparity.

== Examples of animals considered negligibly senescent ==

==== Naked mole rat (Heterocephalus glaber) ====
The naked mole rat<ref>Buffenstein, R. (2008). Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. ''Journal of Comparative Physiology B'', ''178''(4), 439-445.

</ref> is the only mammal known to meet all three criteria of negligible senescence:

''1. No age-related increases in disease incidence and associated death rate:''

In the first two months of life babies are at increased risk of death from inadequate maternal care, cannibalism by siblings and poor inoculation of gastrointestinal flora and fauna. However, after this initial period the rate of death by natural causes is distributed randomly among all age groups rather than showing any age-related increase, except towards the end of the maximum species life span (i.e. the longest a member of the species has been observed to live), when there is believed to be a sudden increase in death rate.

''2. No decrease in reproductive capability:''

Breeding females show no menopause or decline in fertility, even after age 30. In fact, litter size tends to increase with age, although the pups born to older breeders are at greater risk of dying before weaning, possibly because of inadequate milk supply or because of greater disturbance to the larger colonies where these older breeders tend to be found.

The long lifespan of breeding females casts doubt on most evolutionary theories of aging, which generally propose that there is a trade-off between fecundity and lifespan, as energy invested in reproduction is not invested in repairing and maintaining the body.

3. ''No deterioration in physiological capacity, such as strength, mobility and sensory acuity:''

Body composition is maintained from age 2 to age 24.

Naked mole rats have low susceptibility to disease. Notably, neoplasm has never been observed in this species.

=== Aldabra giant tortoise ===
Maximum observed life span: 255 years

=== Rougheye rockfish (Sebastes aleutianus) ===
Maximum observed lifespan: 205 years

=== Lobster ===
Scientists do not currently have a way of establishing the age of lobsters with certainty, but it has been estimated<ref>https://cdnsciencepub.com/doi/abs/10.1139/f99-116</ref> that male European lobsters in the wild have an average life span of 31 years and a maximum of 42 ± 5, while females have an average life span of 54 years and a maximum of 72 ± 9.

=== Lake sturgeon (Acipenser fulvescens) ===
Maximum observed life span: 152 years

=== Ocean quahog (Arctica islandica) ===
Bivalve molluscs <ref>Stenvinkel, P., & Shiels, P. G. (2019). Long-lived animals with negligible senescence: clues for ageing research. ''Biochemical Society Transactions'', ''47''(4), 1157-1164.</ref>provide the widest range of lifespans available for interspecies comparisons. The maximal lifespan in different populations of bivalve molluscs ranges from 36 for the Atlantic surfclam (Spisula solidissima) to >500 years for the ocean quahog (Arctica islandica), despite the similar size and living conditions. (Age is counted by growth rings on the shell).

=== Sea urchin ===
Sea urchins<ref>Bodnar, A. G. (2015). Cellular and molecular mechanisms of negligible senescence: insight from the sea urchin. Invertebrate reproduction & development, 59(sup1), 23-27. </ref> are widely used as model organisms for scientific research, part of their value being their close phylogenetic relationship to humans.

Sea urchins grow throughout their lives and can regenerate damaged appendages. Neoplasm is rare in these animals.

Some species of sea urchins show negligible senescence, and among these species there is a wide variation in maximum life span, ranging from 4 years (Lytechinus variegatus) to 100 years (Strongylocentrotus franciscanus).

Comparison between sea urchin species that show negligible senescence and those that do not and between species with different maximum life spans provides a useful opportunity to investigate factors affecting both aging and life span.

Studies of negligibly senescent sea urchins, of various species and with a range of maximum life spans, have shown maintenance of:

* telomeres;
* antioxidant and proteasome enzyme activities;
* cellular pathways involved in energy metabolism, protein homeostasis and tissue regeneration

They have also shown a lack of major age-related accumulation of oxidative cellular damage.

The findings suggest that negligible senescence relies on the maintenance of mechanisms that sustain tissue homeostasis and regenerative capacity.

== Strategies for engineered negligible senescence (SENS)<ref>Zealley, B., & De Grey, A. D. (2013). Strategies for engineered negligible senescence. Gerontology, 59(2), 183-189. </ref> ==
Achieving (‘engineering’) negligible senescence in humans would not necessarily require damage to be prevented; rather, it would entail repairing damage as it occurs, rapidly and effectively enough that the functioning of the whole organism is not compromised – just as a vintage car can be kept in good working order if wear and tear is regularly repaired.

=== Where in the aging process to intervene in order to engineer negligible senescence ===
Aging can be modelled as a three-stage process:

# '''Metabolism:''' Metabolic processes produce toxins, some of which are not completely removed by the body’s repair mechanisms.
# '''Damage:''' As the toxins accumulate, they cause damage.
# '''Pathology:''' The damage caused by the toxins drives age-related pathologies

Negligible senescence could be engineered by interrupting one of these stages.

Stage 1 (metabolism) and stage 3 (pathology) are difficult to intervene in because they are dynamic processes where an intervention can set off a cascade of results.

Stage 2 (damage) is a simpler target for intervention. This is because although damage itself can also cause dynamic reactions, ''removing'' damage is unlikely to do so. Furthermore, acting on stage 2 does not require an in-depth understanding of stages 1 and 3.

Intervening in stage 2 requires identifying types of damage for which intervention might be needed. As such damage is age-related, a useful way to identify it is to compare the damage found in young people with that found in older people.

Such damage appears to fall into seven categories:

# Cell loss
# Cell death resistance
# Cell overproliferation
# Intracellular ‘junk’
# Extracellular junk
# Tissue stiffening
# Mitochondrial defects

Efforts to develop strategies for engineered negligible senescence therefore focus on methods for mitigating each of the above types of damage, using either existing biotechnology or plausible extensions of it.

=== Why engineer negligible senescence? ===

# Compassionate motives: age-related deterioration has a negative impact on quality of life.
# Economic motives: resources have to be dedicated to supporting those suffering from age-related deterioration. The deterioration also compromises their ability to carry out productive work.

== Implications of deploying anti-senescence technologies widely ==
Widespread deployment of anti-senescence technologies would cause populations to surge. <ref><nowiki>https://www.sciencedirect.com/science/article/pii/S0040162515001985</nowiki> </ref>

==== Advantages ====

* The labor force would be larger and, on average, healthier, which would boost economic growth.

==== Disadvantages ====

* The cost of implementing the anti-senescence technologies could still outweigh the resulting economic growth in some countries.
* In order to finance citizens’ longer lives, governments would have to restructure their financing.
* It might be necessary to eliminate retirement.
* There would be much greater pressure on the environment.

<references />
[[Category:Longevity]]

Negligible senescence

2021-08-11T18:18:00Z

LM: Added section on sea urchins

== Definition ==
Negligible senescence refers to an absence of gradual deterioration with age, specifically an absence of:

# age-related increases in disease incidence and associated death rate;
# decrease in reproductive capability; and
# deterioration in physiological capacity, such as strength, mobility and sensory acuity.

It should be noted that negligible senescence is not synonymous with immortality. An organism that displays negligible senescence - i.e. no gradual deterioration - can still die of a sudden process, whether internal or external, such as predator attack, accident, starvation, exposure to adverse environmental conditions, disease or semelparity.

== Examples of animals considered negligibly senescent ==

==== Naked mole rat (Heterocephalus glaber) ====
The naked mole rat is the only mammal known to meet all three criteria of negligible senescence:

''1. No age-related increases in disease incidence and associated death rate:''

In the first two months of life babies are at increased risk of death from inadequate maternal care, cannibalism by siblings and poor inoculation of gastrointestinal flora and fauna. However, after this initial period the rate of death by natural causes is distributed randomly among all age groups rather than showing any age-related increase, except towards the end of the maximum species life span (i.e. the longest a member of the species has been observed to live), when there is believed to be a sudden increase in death rate.

''2. No decrease in reproductive capability:''

Breeding females show no menopause or decline in fertility, even after age 30. In fact, litter size tends to increase with age, although the pups born to older breeders are at greater risk of dying before weaning, possibly because of inadequate milk supply or because of greater disturbance to the larger colonies where these older breeders tend to be found.

The long lifespan of breeding females casts doubt on most evolutionary theories of aging, which generally propose that there is a trade-off between fecundity and lifespan, as energy invested in reproduction is not invested in repairing and maintaining the body.

3. ''No deterioration in physiological capacity, such as strength, mobility and sensory acuity:''

Body composition is maintained from age 2 to age 24.

Naked mole rats have low susceptibility to disease. Notably, neoplasm has never been observed in this species.

=== Aldabra giant tortoise ===
Maximum observed life span: 255 years

=== Rougheye rockfish (Sebastes aleutianus) ===
Maximum observed lifespan: 205 years

=== Lobster ===
Scientists do not currently have a way of establishing the age of lobsters with certainty, but it has been estimated<ref>https://cdnsciencepub.com/doi/abs/10.1139/f99-116</ref> that male European lobsters in the wild have an average life span of 31 years and a maximum of 42 ± 5, while females have an average life span of 54 years and a maximum of 72 ± 9.

=== Lake sturgeon (Acipenser fulvescens) ===
Maximum observed life span: 152 years

=== Ocean quahog (Arctica islandica) ===
Bivalve molluscs provide the widest range of lifespans available for interspecies comparisons. The maximal lifespan in different populations of bivalve molluscs ranges from 36 for the Atlantic surfclam (Spisula solidissima) to >500 years for the ocean quahog (Arctica islandica), despite the similar size and living conditions. (Age is counted by growth rings on the shell). <ref>Stenvinkel, P., & Shiels, P. G. (2019). Long-lived animals with negligible senescence: clues for ageing research. ''Biochemical Society Transactions'', ''47''(4), 1157-1164.</ref>

=== Sea urchin ===
Sea urchins<ref>Bodnar, A. G. (2015). Cellular and molecular mechanisms of negligible senescence: insight from the sea urchin. Invertebrate reproduction & development, 59(sup1), 23-27. </ref> are widely used as model organisms for scientific research. Part of their value is their close phylogenetic relationship to humans.

Some species of sea urchins show negligible senescence. Different species have considerably differing maximum life spans, ranging from 4 to 100 years. Comparison between species with different maximum life spans provides a useful opportunity to investigate factors affecting both life span and negligible senescence.

Studies of negligibly senescent sea urchins have shown maintenance of:

* telomeres;
* antioxidant and proteasome enzyme activities;
* cellular pathways involved in energy metabolism, protein homeostasis and tissue regeneration

They have also shown a lack of major age-related accumulation of oxidative cellular damage.

These findings were true of various sea urchin species with a range of maximum life spans.

The findings suggest that negligible senescence relies on the maintenance of mechanisms that sustain tissue homeostasis and regenerative capacity.

== Strategies for engineered negligible senescence (SENS)<ref>Zealley, B., & De Grey, A. D. (2013). Strategies for engineered negligible senescence. Gerontology, 59(2), 183-189. </ref> ==
Achieving (‘engineering’) negligible senescence in humans would not necessarily require damage to be prevented; rather, it would entail repairing damage as it occurs, rapidly and effectively enough that the functioning of the whole organism is not compromised – just as a vintage car can be kept in good working order if wear and tear is regularly repaired.

=== Where in the aging process to intervene in order to engineer negligible senescence ===
Aging can be modelled as a three-stage process:

# '''Metabolism:''' Metabolic processes produce toxins, some of which are not completely removed by the body’s repair mechanisms.
# '''Damage:''' As the toxins accumulate, they cause damage.
# '''Pathology:''' The damage caused by the toxins drives age-related pathologies

Negligible senescence could be engineered by interrupting one of these stages.

Stage 1 (metabolism) and stage 3 (pathology) are difficult to intervene in because they are dynamic processes where an intervention can set off a cascade of results.

Stage 2 (damage) is a simpler target for intervention. This is because although damage itself can also cause dynamic reactions, ''removing'' damage is unlikely to do so. Furthermore, acting on stage 2 does not require an in-depth understanding of stages 1 and 3.

Intervening in stage 2 requires identifying types of damage for which intervention might be needed. As such damage is age-related, a useful way to identify it is to compare the damage found in young people with that found in older people.

Such damage appears to fall into seven categories:

# Cell loss
# Cell death resistance
# Cell overproliferation
# Intracellular ‘junk’
# Extracellular junk
# Tissue stiffening
# Mitochondrial defects

Efforts to develop strategies for engineered negligible senescence therefore focus on methods for mitigating each of the above types of damage, using either existing biotechnology or plausible extensions of it.

=== Why engineer negligible senescence? ===

# Compassionate motives: age-related deterioration has a negative impact on quality of life.
# Economic motives: resources have to be dedicated to supporting those suffering from age-related deterioration. The deterioration also compromises their ability to carry out productive work.

== Implications of deploying anti-senescence technologies widely ==
Widespread deployment of anti-senescence technologies would cause populations to surge. <ref><nowiki>https://www.sciencedirect.com/science/article/pii/S0040162515001985</nowiki> </ref>

==== Advantages ====

* The labor force would be larger and, on average, healthier, which would boost economic growth.

==== Disadvantages ====

* The cost of implementing the anti-senescence technologies could still outweigh the resulting economic growth in some countries.
* In order to finance citizens’ longer lives, governments would have to restructure their financing.
* It might be necessary to eliminate retirement.
* There would be much greater pressure on the environment.

<references />
[[Category:Longevity]]

Negligible senescence

2021-07-18T20:35:30Z

LM:

== Definition ==
Negligible senescence refers to an absence of gradual deterioration with age, specifically an absence of:

# age-related increases in disease incidence and associated death rate;
# decrease in reproductive capability; and
# deterioration in physiological capacity, such as strength, mobility and sensory acuity.

It should be noted that negligible senescence is not synonymous with immortality. An organism that displays negligible senescence - i.e. no gradual deterioration - can still die of a sudden process, whether internal or external, such as predator attack, accident, starvation, exposure to adverse environmental conditions, disease or semelparity.

== Examples of animals considered negligibly senescent ==

==== Naked mole rat (Heterocephalus glaber) ====
The naked mole rat is the only mammal known to meet all three criteria of negligible senescence:

''1. No age-related increases in disease incidence and associated death rate:''

In the first two months of life babies are at increased risk of death from inadequate maternal care, cannibalism by siblings and poor inoculation of gastrointestinal flora and fauna. However, after this initial period the rate of death by natural causes is distributed randomly among all age groups rather than showing any age-related increase, except towards the end of the maximum species life span (i.e. the longest a member of the species has been observed to live), when there is believed to be a sudden increase in death rate.

''2. No decrease in reproductive capability:''

Breeding females show no menopause or decline in fertility, even after age 30. In fact, litter size tends to increase with age, although the pups born to older breeders are at greater risk of dying before weaning, possibly because of inadequate milk supply or because of greater disturbance to the larger colonies where these older breeders tend to be found.

The long lifespan of breeding females casts doubt on most evolutionary theories of aging, which generally propose that there is a trade-off between fecundity and lifespan, as energy invested in reproduction is not invested in repairing and maintaining the body.

3. ''No deterioration in physiological capacity, such as strength, mobility and sensory acuity:''

Body composition is maintained from age 2 to age 24.

Naked mole rats have low susceptibility to disease. Notably, neoplasm has never been observed in this species.

=== Aldabra giant tortoise ===
Maximum observed life span: 255 years

=== Rougheye rockfish (Sebastes aleutianus) ===
Maximum observed lifespan: 205 years

=== Lobster ===
Scientists do not currently have a way of establishing the age of lobsters with certainty, but it has been estimated<ref>https://cdnsciencepub.com/doi/abs/10.1139/f99-116</ref> that male European lobsters in the wild have an average life span of 31 years and a maximum of 42 ± 5, while females have an average life span of 54 years and a maximum of 72 ± 9.

=== Lake sturgeon (Acipenser fulvescens) ===
Maximum observed life span: 152 years

=== Ocean quahog (Arctica islandica) ===
Bivalve molluscs provide the widest range of lifespans available for interspecies comparisons. The maximal lifespan in different populations of bivalve molluscs ranges from 36 for the Atlantic surfclam (Spisula solidissima) to >500 years for the ocean quahog (Arctica islandica), despite the similar size and living conditions. (Age is counted by growth rings on the shell). <ref>Stenvinkel, P., & Shiels, P. G. (2019). Long-lived animals with negligible senescence: clues for ageing research. ''Biochemical Society Transactions'', ''47''(4), 1157-1164.</ref>

== Strategies for engineered negligible senescence (SENS)<ref>Zealley, B., & De Grey, A. D. (2013). Strategies for engineered negligible senescence. Gerontology, 59(2), 183-189. </ref> ==
Achieving (‘engineering’) negligible senescence in humans would not necessarily require damage to be prevented; rather, it would entail repairing damage as it occurs, rapidly and effectively enough that the functioning of the whole organism is not compromised – just as a vintage car can be kept in good working order if wear and tear is regularly repaired.

=== Where in the aging process to intervene in order to engineer negligible senescence ===
Aging can be modelled as a three-stage process:

# '''Metabolism:''' Metabolic processes produce toxins, some of which are not completely removed by the body’s repair mechanisms.
# '''Damage:''' As the toxins accumulate, they cause damage.
# '''Pathology:''' The damage caused by the toxins drives age-related pathologies

Negligible senescence could be engineered by interrupting one of these stages.

Stage 1 (metabolism) and stage 3 (pathology) are difficult to intervene in because they are dynamic processes where an intervention can set off a cascade of results.

Stage 2 (damage) is a simpler target for intervention. This is because although damage itself can also cause dynamic reactions, ''removing'' damage is unlikely to do so. Furthermore, acting on stage 2 does not require an in-depth understanding of stages 1 and 3.

Intervening in stage 2 requires identifying types of damage for which intervention might be needed. As such damage is age-related, a useful way to identify it is to compare the damage found in young people with that found in older people.

Such damage appears to fall into seven categories:

# Cell loss
# Cell death resistance
# Cell overproliferation
# Intracellular ‘junk’
# Extracellular junk
# Tissue stiffening
# Mitochondrial defects

Efforts to develop strategies for engineered negligible senescence therefore focus on methods for mitigating each of the above types of damage, using either existing biotechnology or plausible extensions of it.

=== Why engineer negligible senescence? ===

# Compassionate motives: age-related deterioration has a negative impact on quality of life.
# Economic motives: resources have to be dedicated to supporting those suffering from age-related deterioration. The deterioration also compromises their ability to carry out productive work.

== Implications of deploying anti-senescence technologies widely ==
Widespread deployment of anti-senescence technologies would cause populations to surge. <ref><nowiki>https://www.sciencedirect.com/science/article/pii/S0040162515001985</nowiki> </ref>

==== Advantages ====

* The labor force would be larger and, on average, healthier, which would boost economic growth.

==== Disadvantages ====

* The cost of implementing the anti-senescence technologies could still outweigh the resulting economic growth in some countries.
* In order to finance citizens’ longer lives, governments would have to restructure their financing.
* It might be necessary to eliminate retirement.
* There would be much greater pressure on the environment.

<references />
[[Category:Longevity]]