WHAT ARE SIRTUINS?

Sirtuins (Silent Information Regulators) are a class of proteins that regulate optimum cellular health. [1]

academic.oup.com/mend/article/21/8/1745/2738297

They are found in healthy cells, but as we age the body produces less and less.

SIRTUINS NEED NAD+ FOR THEIR FORMATION [2]

anti-agingfirewalls.com/2014/11/11/nad-an-emerging-framework-for-life-extension-part-1-the-nad-world-2/

Sirtuins (SIRT1-SIRT7) perform a variety of functions essential for cellular health.

Some target transcription regulation, others healthy inflammatory response  and metabolism [3]

pdb101.rcsb.org/motm/213

 

WHAT DO SIRTUINS DO?

Sirtuins influence and help a wide range of healing processes in the body [4]

ncbi.nlm.nih.gov/pubmed/23325925

They are found in healthy cells, but as we age the body produces less and less.

Increasing levels of NAD+ is as one ages is very important.

NAD+ supplementation - MAIN MECHANISM to Increasing SIRTUIN ACTIVITY

Towards the OPTIMUM LEVELS from our Youth.

Scientific evidence shows sirtuins are important energy status sensors.

Sirtuins also protect cells against metabolic stresses.

Sirtuins are understood to regulate the aging process.2

SIRT bound to NAD: [5] 

pdb101.rcsb.org/motm/213

                                                              

SIRT1

Is an enzyme which is crucial in single and double strand DNA break repair.[6]

ncbi.nlm.nih.gov/pmc/articles/PMC3943707

SIRT1 ACTIVITY IS NEUROPROTECTIVE[7]

nature.com/articles/s41419-018-0553-6

 

SIRT3 

Is critical for maintaining mitochondrial integrity and function.

Can regulate cell survival, death and metabolic pathways.

Helping to control the balance between health and disease.

 

SIRT6 

Protects against aging-associated pathologies.

Chromatin regulation by SIRT6 maintains stem cell homeostasis and function.

This suggests that SIRT6 opposes aging-related stem cell dysfunction. [8]

cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(16)30127-8

 

NAD+, SIRTUINS & AGING

Recent scientific studies are showing optimum levels of NAD+ and sirtuins are crucial for healthy aging.

Research is pointing to the use of sirtuins as a powerful tool in anti-aging medicine/approaches

INCREASING LEVELS OF NAD+ IS CONSIDERED ONE OF THE MAIN ROUTES. [9]

ncbi.nlm.nih.gov/pmc/articles/PMC5514220/

It has also been demonstrated that NAD+ decreases as we age reducing sirtuin activity

 

Reduced sirtuin activity:

  • Disrupts communication between the nucleus and mitochondria at a cellular level
  • Disrupts communication between the hypothalamus and fat tissue at a systemic level.[10]

 nature.com/articles/npjamd201617

Sirtuins are important in:

  • Supporting healthy inflammatory system
  • Energy efficiency
  • Mitochondrial regulation
  • Circadian rhythm (the bodies biological clock)
  • Aging [11]

 ncbi.nlm.nih.gov/pmc/articles/PMC2922851/

SIRTUIN TYPES

 

Location
Activity
Function
SIRT1

Nucleus

Deacetylase

Metabolism, inflammatory response, neurone health

SIRT2

Cytoplasma

Deacetylase

Cell cycle

SIRT3

Nucleus, mitochondria

Deacetylase

Metabolism

SIRT4

Mitochondria

ADP-ribosylation

Insulin secretion

SIRT5

Mitochondria

Deacetylase

Unknown

SIRT6

Nucleus

ADP-ribosylation

DNA repair

SIRT7

Nucleus

Unknown

rDNA transcription

 

[12] 

academic.oup.com/mend/article/21/8/1745/2738297


SIRTUIN’S ROLE IN AGING

[13]

academic.oup.com/mend/article/21/8/1745/2738297


Protective Sirtuins
protect the body from age-related problems.

THE IMPORTANCE OF NAD+ & SIRTUINS IN MITOCHONDRIAL REGULATION [14]

nature.com/articles/npjamd201617

SIRTUIN MECHANISM OF ACTION

DEACETYLATION [15]

sciencedirect.com/science/article/pii/B9780128053881000134

Removal of acetyl group from protein.

This process is important in gene regulation and is NAD DEPENDANT.

ADP-RIBOSYLATION [16]:

mmbr.asm.org/content/70/3/789

Addition of ADP-ribose moieties to protein.

Important in cell signalling and DNA repair and is NAD DEPENDANT.

 

CONCLUSION

Supplementation of key NAD+ precursors can

ACTIVATE SIRTUINS AND REGULATE CELL HEALTH.

 

[1] academic.oup.com/mend/article/21/8/1745/2738297

[2] anti-agingfirewalls.com/2014/11/11/nad-an-emerging-framework-for-life-extension-part-1-the-nad-world-2/

[3] pdb101.rcsb.org/motm/213

[4] ncbi.nlm.nih.gov/pubmed/23325925

[5] pdb101.rcsb.org/motm/213

[6] ncbi.nlm.nih.gov/pmc/articles/PMC3943707

[7] nature.com/articles/s41419-018-0553-6

[8] cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(16)30127-8

[9] ncbi.nlm.nih.gov/pmc/articles/PMC5514220/

[10] nature.com/articles/npjamd201617

[11] ncbi.nlm.nih.gov/pmc/articles/PMC2922851/

[12] academic.oup.com/mend/article/21/8/1745/2738297

[13] jci.org/articles/view/64094/figure/1

[14] nature.com/articles/npjamd201617

[15] sciencedirect.com/science/article/pii/B9780128053881000134

[16] mmbr.asm.org/content/70/3/789