Exploring the code of life: the wonderful anti-aging journey of α-ketoglutarate (AKG) and longevity protein SIRT5

In the grand landscape of life sciences, the exploration of aging mechanisms has always occupied a core position. In recent years, research results on α-ketoglutarate (AKG) and longevity protein SIRT5 have revealed a new anti-aging pathway for us. They are like key gears in a precise clock, jointly regulating cell metabolism and function, delaying aging process.

1. Longevity protein: the guardian of cell youth

There are seven groups of longevity proteins SIRT1-SIRT7 in the human body are like "smart housekeepers" within cells, playing an irreplaceable role in many key processes such as cell metabolism, aging, and apoptosis.

1) SIRT1: The regulator of metabolism

SIRT1 regulates cellular metabolism through deacetylation modification of a variety of transcription factors and enzymes. Under energy limitation conditions, SIRT1 is activated to enhance the cell's utilization efficiency of nutrients and maintain the energy balance of the cell. It is like a careful housekeeper who reasonably plans the "income and expenditure" of the cell to ensure that the cell can survive in various environments. Can operate stably.

2) SIRT2: The precise controller of the cell cycle

SIRT2 is mainly involved in the regulation of the cell cycle. It regulates the expression of cyclin-dependent kinase inhibitors and ensures orderly cell division. When cells are damaged or aged, SIRT2 can prevent the proliferation of abnormal cells and maintain the health of the cell population by regulating the cell cycle.

3) SIRT3: Maintainer of mitochondrial energy factory

Mitochondria serve as the "energy factory" of cells, and the normal maintenance of their functions is crucial to cells. SIRT3 is located in mitochondria and participates in mitochondrial energy metabolism. It modifies key enzymes in mitochondria by deacetylation, such as pyruvate dehydrogenase complex, etc., thereby enhancing the respiratory function of mitochondria, improving the efficiency of ATP generation, and ensuring sufficient energy supply for cells.

4) SIRT4: The balance messenger of amino acid metabolism

SIRT4 plays a key role in amino acid metabolism. It can regulate the activity of enzymes related to amino acid metabolism, control the decomposition and synthesis of amino acids, and maintain the balance of amino acids in cells. This balance is critical for protein synthesis, cell growth and repair.

5) SIRT5: Metabolic all-rounder and anti-aging upstart

SIRT5 not only regulates urea cycle and fatty acid metabolism, but also exhibits unique functions in the anti-aging process. In the urea cycle, it modifies key enzymes through desuccinylation, enhances urea synthesis efficiency, maintains nitrogen balance in the body, and reduces the toxicity of ammonia to cells. In terms of fatty acid metabolism, SIRT5 activates CPT2, promotes the entry of fatty acids into mitochondria for oxidation, and at the same time reduces the activity of fatty acid synthase, prevents excessive accumulation of fat, and reduces damage to cells caused by lipotoxicity, thereby maintaining the normal function of cells and delaying cell aging.

6) SIRT6: The loyal guardian of the genome

SIRT6 participates in the DNA repair process and can identify and repair damaged DNA. As we age, DNA damage gradually accumulates, and the existence of SIRT6 is like a dedicated "DNA repair craftsman", repairing damage in a timely manner, maintaining the stability of the genome, and reducing cell aging and lesions caused by DNA damage.

7) SIRT7: Regulator of ribosome production

SIRT7 is involved in the ribosome DNA transcription process. Ribosomes are the key site for protein synthesis. SIRT7 affects the synthesis rate and quality of intracellular proteins by regulating the synthesis of ribosomes, ensuring that cells can function normally. Growth, differentiation and repair, maintaining normal physiological functions of cells.

2. AKG: the energy link for cellular anti-aging

As a key node in the cellular metabolic network, α-ketoglutarate(AKG) plays an important role in many aspects of the anti-aging process.

1) Core participant in energy metabolism

AKG is a key intermediate product of the tricarboxylic acid cycle. It is continuously oxidized and decomposed during the cycle to provide cells with a large amount of energy. At the same time, AKG can also provide energy for other metabolic processes through indirect pathways and maintain cellular energy homeostasis. When the energy level of cells decreases, the content of AKG will be adjusted accordingly, activating a series of energy production pathways to ensure that cells have enough energy to carry out normal physiological activities and avoid accelerated cell aging caused by insufficient energy.

2) Pioneer in anti-oxidative stress

AKG can activate intracellular antioxidant enzyme systems, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), etc. These antioxidant enzymes can remove excessive reactive oxygen species (ROS) produced in cells and reduce the damage caused by oxidative stress to cells. Oxidative stress is one of the important factors leading to cellular aging. AKG effectively delays the cellular aging process by enhancing the antioxidant capacity of cells.

3. The synergistic anti-aging symphony of AKG and SIRT5

1) Anti-aging cooperation in the urea cycle

In the urea cycle, AKG not only indirectly supplies energy, but also provides raw materials. SIRT5 modifies key enzymes in the urea cycle through desuccinylation, enhances the activity of these enzymes, and improves urea synthesis efficiency. The two work synergistically to maintain nitrogen balance in the body and reduce the accumulation of ammonia in the body. The accumulation of ammonia can cause toxicity to cells, damage cell functions, and accelerate cell aging. AKG and SIRT5 play an anti-aging role by maintaining nitrogen balance and protecting cells from ammonia toxicity.

2) Regulation of fat metabolism helps resist aging

In terms of fat metabolism, AKG participates in the tricarboxylic acid cycle and provides energy for fatty acid oxidation. At the same time, AKG can also activate the AMPK signaling pathway and inhibit fat synthesis. SIRT5 activates CPT2 to promote fatty acids to enter mitochondria for oxidation and reduce intracellular fat accumulation. In addition, SIRT5 can also reduce the activity of fatty acid synthase and further inhibit fat synthesis. Excessive fat accumulation can trigger an inflammatory response, produce a large amount of ROS, and lead to cell senescence. AKG and SIRT5 jointly regulate fat metabolism, reduce fat accumulation and lipotoxicity, reduce inflammation and oxidative stress, and delay cell aging.

3) Anti-aging effect of enzyme activity regulation

AKG can be used as an allosteric activator or substrate of enzymes to regulate enzyme activity. SIRT5 changes the structure and active site of the enzyme by modifying the enzyme, affecting the function of the enzyme. For example, in the antioxidant defense system, AKG activates antioxidant enzymes, SIRT5 modifies catalase, etc. The two work synergistically to enhance the antioxidant capacity of cells and reduce oxidative stress damage. Oxidative stress is an important factor leading to cellular aging. By reducing oxidative stress, AKG and SIRT5 effectively delay cellular aging.

4) The anti-aging significance of metabolic pathway integration

As a key node of the tricarboxylic acid cycle, AKG connects multiple metabolic pathways to provide energy for cells. SIRT5 regulates the activity of mitochondrial metabolic enzymes and optimizes mitochondrial energy production efficiency. The two work together to maintain the energy homeostasis of cells, ensuring that cells have enough energy to carry out normal physiological activities and resist aging. In terms of amino acid metabolism, AKG participates in the metabolic process of amino acids, and SIRT5 regulates the activity of related enzymes to maintain amino acid balance. Amino acid balance is essential for protein synthesis and cell repair, helping to maintain normal cell function and delay cell aging. In addition, AKG activates the AMPK signaling pathway and SIRT5 modifies key proteins in the pathway. The two jointly regulate physiological activities such as cell growth, proliferation, and metabolism, and achieve anti-aging effects by optimizing cell physiological functions.

AKG and longevity protein SIRT5 work closely together at all levels of cell metabolism to weave a powerful anti-aging network. They maintain the health and vitality of cells from multiple perspectives such as energy supply, metabolic balance, and oxidative stress defense, and reveal the inner secret of cells to delay aging. As Shaanxi Derivative's research on them continues to deepen, it is expected to bring more hope and possibilities to human health and longevity, and start a new anti-aging revolution.