The basis of human longevity and healthy aging, and how to achieve these desirable phenotypes, remain among the principal challenges of biology and medicine. To start to understand longevity, you have to get to know main biological factors: telomeres, NAD+ molecules, sirtuin genes, AMPK and mTOR biological pathways, epigenetic clock and the influence of senescent cells. Analysis and monitoring of these lets you see your quality of lifespan and your youthfulness status.
Telomeres represent your biological age.
NAD+ molecule shows your youthful status.
Sirtuin genes, AMPK, and mTOR control your biological pathways of longevity.
Epigenetic clock: a new aging clock?
The aging process accumulates senescent cells.
Let’s walk through each.
A telomere is a region of repetitive DNA sequences at the end of a chromosome.
Telomeres protect the ends of chromosomes from becoming frayed or tangled. During our lifespan, telomeres become shorter. This is a natural process, which is initiated when cells divide. Still when telomeres become too short, the cells die.
Telomeres are a very good and precise indicator of how our body and cells are aging. It is known that the average length of telomeres is about eight to 17 kilobases (one base is one structural unit of our DNA). Newborns have long telomeres of 15 to 17 kilobases, middle aged people have 11 to 12 kilobases and older people have eight to 10 kilobases of telomere length.
The human body has an enzyme called telomerase. Telomerase has an ability to stabilize and extend telomeres.
Nicotinamide adenine dinucleotide (NAD+)
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme present in all living cells in the human body. NAD+ plays a lot of roles in the cell’s life.
This molecule is responsible for the youthfulness of our cells. It also plays a key role for boosting energy and upregulating cellular repair. During the aging process, NAD+ level decreases. For example, newborns have 8.5 NAD+ average concentration, middle-aged people have 2.74 and older ones about 1.08 (Massudi et al., 2012).
Studies on ageing in model systems have revealed a class of proteins termed sirtuins. In humans there are seven proteins belonging to the sirtuin family. Modulation of sirtuin activity in humans can regulate many processes such as gene expression, cell metabolism, apoptosis, DNA repair, cell cycle, development, immune response and neuroprotection.
The anti-ageing action of sirtuins appears to be the new scientific field of longevity.
Overexpression of some sirtuins has been shown to extend lifespan in several organisms. The suppression of cellular senescence by sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promoting DNA damage repair.
Although there has been emerging debate on the role of sirtuins in ageing and lifespan extension, mounting evidence suggests that sirtuins are indeed the critical modulators of ageing and ageing-related diseases via different signalling pathways.
AMPK biological pathway
AMP activated protein kinase (AMPK) activity can extend the lifespan of some model organisms. AMPK can regulate cellular energy status through modulation of NAD+ level, which suggests that this kinase may be involved in regulation of sirtuin activity.
AMPK is a sensor of cellular energy status and a critical regulator of cellular homeostasis, metabolism response to stress, oxidative damage and many other processes involved in ageing.
AMPK activation and AMPK responsiveness decrease with age, so finding efficient strategies of increasing AMPK responsiveness and activation may be of important use as anti-ageing treatments and for lifespan elongation.
mTOR biological pathway
The mammalian/mechanistic target of rapamycin (mTOR) is a key component of cellular metabolism that integrates nutrient sensing with cellular processes that fuel cell growth and proliferation.
Involvement of the mTOR pathway in regulating life span and ageing has been studied extensively in the last decade. mTOR is considered an important regulator of oxidative stress by promoting mitochondrial biogenesis. mTOR is a key player in the activation of tissue stem cells which contributes to tissue repair.
Human DNA and genome are not alone and they could be controlled by epigenetics.
Epigenetics is a process when epigenetic factors (methylation groups) could activate/inhibit our genes. It is the natural biological pathway of our organism to control our genes and make a response to environmental stress.
Today, it is possible to collect epigenetic factors from the blood and calculate when the cells will be lacking them. From these calculations it is possible to see the epigenetic clock of humans.
With age, senescent cells accumulate in many tissues, impairing their proper functioning.
Senescent cells have a strong impact on surrounding cells. They modify the microenvironment by secreting certain cytokines, chemokines and mediators of inflammation.
Senescent cells could damage DNA in live cells. It could be the factor of destabilization of telomeres. The negative roles of senescent cells are degradation of proteins and initiating changes of mitochondria in the cells around them. Live and young cells become affected and can start to be senescent, too.
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The factors mentioned above are the main genetic-biological players that are involved in our longevity. When we control our habits, we can control, restore and stabilize our biological longevity factors – increase NAD+ level, stabilize/extend telomeres, activate mTOR, AMPK cellular pathways, and turn back our epigenetic clock.
- Cancers. Telomeres and Telomere Length: A General Overview.
- National Library of Medicine. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.
- Chinese Medical Journal. Sirtuins Function as Modulators in Aging-related Diseases in Common or Respectively.
- Discoveries. AMPK activation can delay aging.
- National Library of Medicine. MTORC1 and the Rebirth of Stemness.
- Aging. DNA methylation GrimAge strongly predicts lifespan and healthspan.
- Nature. To stay young, kill zombie cells.
- National Library of Medicine. The role and biology of senescent cells in ageing-related tissue damage and repair.