According to TCM, aging is due to the decline in “Primordial Qi”. To stay healthy, it is important to prevent the excessive loss of “Primordial Qi”. “Primordial Qi” cannot be replenished later in life, so the focus should be on reducing its loss rate. Factors like insufficient “Acquired Qi” and/or unhealthy “Zang-Fu” organs can accelerate the loss. Therefore, the key to staying healthy is to preserve “Primordial Qi” and nourish “Acquired Qi” [17] [19] .

To delay aging and prevent age-related diseases, it is crucial to continuously generate enough “Zheng Qi” ( Figure 2 ) [35] . “Zheng Qi” is created by combining “Primordial Qi” and “Acquired Qi”. “Primordial Qi” is given by our parents and cannot be replenished later in life. “Acquired Qi” can come from the air we breathe and the food we eat. If the production of “Acquired Qi” is reduced due to the “deficiency” in body functions, and more “Primordial Qi” is needed to create “Zheng Qi”, the consumption rate of “Primordial Qi” will increase. On the other hand, if enough “Acquired Qi” is produced, the consumption rate of “Primordial Qi” is normal [36] . Therefore, using Chinese tonifying herbs to maintain the normal functions of the “Zang-Fu” organs can slow down the consumption of “Primordial Qi” and thereby delay the aging process ( Figure 2 ) [37] - [39] . In this regard, it has been shown that seven TCM herbal extracts can enhance the ergogenic capacity in aged mice [40] .

According to TCM, effective communication between the “Zang Xiang system” and the “anatomical physiological system” is crucial for good health [3] . However, human thoughts and desires can hinder this communication, thus affecting physical health [41] . Religious beliefs aim to calm people down in response to this issue. Chinese Qigong exercises and postures are methods to help people achieve calmness [42] . When unnecessary thoughts and desires are eliminated, the barrier between the two life systems will naturally break down, allowing communication between the “Zang Xiang system” and the “anatomical physiological system”. This is known as the “unity of man and nature” [41] [43] .

Maintain mitochondrial energy-producing and signaling function

Strategies to treat aging problems should focus on addressing root causes, as this is more effective than dealing with the consequences. However, current medical technologies used to treat age-related diseases have not addressed the underlying causes of aging. This is why these therapies have limited effectiveness. One important underlying cause of aging is the rate of mitochondrial ROS production (mtROSp) [32] . As cells and organisms age, the respiratory chain becomes less effective, leading to increased electron leakage and reduced ATP production. To compensate by increasing electron transport, the level of ROS production continues to rise with age, causing more oxidative damage to mitochondria [44] .

Recent research has consistently shown that mtROS is an important signaling molecule that causes changes in cells and the body. ROS can stimulate cells' antioxidant response and protect mitochondria through reverse signal transmission [45] . However, aging can lead to oxidative damage in mitochondria due to a lack of sufficient response to endogenous ROS signaling [46] . Studies have found that compounds like metformin and resveratrol can induce a low-energy state and trigger mitochondrial stress response by increasing AMP levels and activating AMPK [47] . This response has been observed in mammals during long-term aerobic exercise, which increases mitochondrial oxygen consumption without causing a harmful increase in mtROS [48] . Like dietary restriction, moderate exercise can slow the effects of aging and extend the average lifespan. However, unlike dieting, exercise does not increase the upper limit of lifespan because it primarily stimulates mitochondrial stress responses in the heart and muscles [48] .

Scientists recommend using mitochondria-targeted antioxidants to protect mitochondria from oxidative damage. However, repeated trials of different targeted antioxidants have been unsatisfactory [45] . This is because these antioxidants non-specifically change the redox balance in mitochondria, causing adverse side effects and affecting mitochondrial-dominated information transmission [49] . To address this issue, scientists have recently studied specific inhibitors that act on specific locations in the mitochondria to prevent the production of mtROS. These inhibitors do not reduce ATP production or disrupt the redox balance within the mitochondria [50] . Preliminary experimental results show that this type of inhibitor can effectively prevent pathological changes caused by mtROS and may also have the potential for testing its impact on aging in the long term.

From the above discussion, we know that aging is often linked to problems with mitochondria, which are the powerhouses of our cells. Scientists are actively looking for compounds that can protect and improve mitochondrial function. However, there is still a lack of safe and effective methods to enhance mitochondrial function, especially a process called mitophagy for removing damaged mitochondria [50] [51] , due to the toxicity and lack of specificity of certain compounds. One promising compound is urolithin A, which can induce mitophagy, extend mitochondrial functional span, and promote healthy aging [52] . Studies have found that urolithin A improves various activities in aging rodents, such as their ability to move and exercise, and helps maintain the function of their mitochondria [53] . It also prevents the age-related loss of muscle function known as sarcopenia, as evidenced by experimental and clinical studies [54] .

Scientists believe that as we age, the number of senescent cells in our body increases, which may contribute to the aging process. These cells release substances that cause inflammation, potentially accelerating aging [30] . Some natural compounds like resveratrol and catechin have been shown to have anti-aging effects, but not all of them reduce senescent cell activity [55] [56] . Fisetin and quercetin have been found to deactivate senescent cells [56] . Many compounds work by reducing oxidative damage in organs rather than directly killing senescent cells. It is expected that more natural compounds will be discovered in the future that can deactivate senescent cells. Recent studies have also found that dietary restriction can help prevent the accumulation of senescent cells in both mice and humans, without harming normal cells [57] [58] .

All living organisms that use oxygen are exposed to harmful substances called oxidants. These oxidants can come from inside the body or from outside sources. To protect themselves from these harmful effects, cells have developed a strong antioxidant system. This system helps maintain a balance between oxidants and antioxidants, which is important for the cell’s survival. When this balance is disrupted and there are more oxidants than antioxidants, it leads to a condition called oxidative stress. Oxidative stress can cause damage to lipids, proteins, and DNA in cells, and has been linked to various diseases like cardiovascular and neurodegenerative diseases, cancer, diabetes, and cataracts. These diseases are often associated with aging [59] [60] .

As we age, the production of harmful oxidants increases, leading to age-related diseases. Our cells rely on a transcription factor called nuclear factor erythroid 2-related factor 2 (Nrf2) to activate the antioxidant defense mechanism [61] . Nrf2 controls how our cells respond to oxidative stress and helps regulate the expression of antioxidant molecules and detoxification enzymes. The Nrf2 signaling system is crucial for our cells’ defense against oxidative stress and toxins [62] . However, as we age, the capacity of the Nrf2-activated antioxidant system decreases, resulting in lower levels of antioxidants and weaker antioxidant responses to oxidative stress [63] .

Glutathione (GSH) is a physiological antioxidant molecule found in cells. As we age, the level of GSH generally decreases. However, cells have systems in place to regulate GSH levels and maintain balance in the short term. These systems may involve the production and regeneration of GSH through specific enzymes [64] [65] . As we get older, the balance shifts towards more oxidative states, with the increased consumption of GSH. This is due to reactions with substances like hydrogen peroxide, lipid hydroperoxides, and electrophilic molecules. Additionally, the activity of enzymes that degrade GSH also increases with age, further contributing to the decrease in GSH levels. Another possible reason for the age-related decrease in GSH is that the system responsible for synthesizing GSH in response to oxidative stress may not function as effectively [66] .

When there is a disturbance in oxidative stress or GSH homeostasis, the body typically responds by increasing GSH production. One way to maintain the cellular GSH antioxidant response to oxidative stress is by using natural compounds like stilbenes, flavonoids, catechins, curcumin, and resveratrol, which can activate Nrf2 and enhance GSH homeostasis [61] [67] . Another safer method to induce antioxidant responses is by stimulating the production of small amounts of endogenous ROS, such as during exercise [48] , and using phytochemicals like ursolic acid and beta-sitosterol to stimulate mitochondrial electron transport and ATP production [68] [69] . The cytochrome P450-catalyzed metabolism of schisandrin B (an active ingredient from Schisandrae Sinensis Fructus) also produces a small amount of ROS, which triggers an antioxidant response [70] [71] . This self-limiting mechanism of stimulating cells’ antioxidant response avoids adverse side effects from overreaction. Furthermore, by inducing the antioxidant response of cells, it can prevent interference with the antioxidant regulation system caused by external antioxidant molecules and inadequate response to oxidative stress.

TCM believes that maintaining health and delaying aging involves preserving “Primordial Qi” and nourishing “Acquired Qi” to support the generation of “Zheng Qi” and hence normal functioning of the “Zang-Fu” organs. Western medicine attributes aging to dysfunction of cell mitochondria, which leads to various aging-related diseases. In this regard, a unifying theory of aging between TCM and Western medicine has been proposed [37] . TCM’s concept of “Zheng Qi” decline in aging is consistent with the “Mitochondrial decay theory in aging”, in that the functional manifestation of “Zheng Qi” can be linked to the generation of ATP by mitochondria. By integrating TCM and Western medicine theories, we can potentially discover ways to effectively delay aging [10] [72] [73] .

Firstly, following TCM theory, we can use Chinese tonifying herbs to support the normal functioning of “Zang and Fu” organs and nourish the “Acquired Qi”. Research shows that natural compounds found in these herbs can also improve mitochondrial dysfunction, which in turn helps prevent cellular aging and age-related diseases [74] [75] . These compounds protect and remove damaged mitochondria by enhancing the oxidative stress response, antioxidant response, and mitophagy activity [74] . Lastly, these safe and effective natural compounds can eliminate senescent cells in various organs and prevent or reduce age-related inflammations [76] [77] .

The integration of TCM and Western medicine can help delay aging. This approach focuses on the “Zang Xiang system” in TCM as well as targets cell mitochondria in Western medicine. By incorporating a balanced and healthy diet, regular exercise, proper work-and-rest balance, and emotional regulation, one can achieve the “unity of nature and man”. This can effectively delay aging and potentially enable individuals to live longer, up to a hundred years old.