From the perspective of current scientific knowledge and technological development, designing humans who will never age technically still faces many insurmountable challenges, but it is possible to explore the possible ways of genetic engineering technology in delaying aging in theory: ### Telomere-related gene regulation 1. **Maintain telomere length** - **Gene editing strategy**: Telomeres are protective structures at the ends of chromosomes. They gradually shorten as cells divide and are closely related to aging. Telomerase genes in cells can be modified through gene editing technologies, such as CRISPR/Cas9. Telomerase can extend telomere length. By enhancing the expression of telomerase genes through genetic engineering, it can maintain the length of telomeres during cell division, thereby delaying cell aging. - **Example**: Studies have found that telomerase activity is relatively high in some long-lived animals. Human cells are genetically modified to make the promoter region of the telomerase gene easier to be activated, or the catalytic subunit of telomerase, TERT, is directly overexpressed. In this way, every time the cell divides, telomerase can replenish the shortened telomere part in time, maintain the stability of the chromosome, and thus delay the aging process of the cell. 2. **Repair telomere damage** - **Gene editing strategy**: In addition to maintaining telomere length, attention should also be paid to telomere damage repair. Genes related to DNA repair can be edited, such as genes involved in homologous recombination repair (HR) and non-homologous end joining (NHEJ) pathways. Enhance the function of these genes so that they can repair DNA damage at telomeres more efficiently and reduce telomere shortening and cell aging caused by damage accumulation. - **Example**: BRCA1 and BRCA2 genes play a key role in the repair of double-strand DNA breaks. Through genetic engineering technology, these genes are optimized for expression, or some small molecule RNAs that can promote the HR pathway are introduced to improve the cell's ability to repair telomere damage. When telomeres are damaged by external factors such as oxidative stress and radiation, cells can quickly initiate effective repair mechanisms to maintain the normal structure and function of telomeres, thereby delaying cell aging. ### Regulating aging-related signaling pathways 1. **Inhibit the mTOR signaling pathway** - **Gene editing strategy**: The mTOR (mammalian target of rapamycin) signaling pathway plays an important regulatory role in cell growth, metabolism and aging. Over-activated mTOR signaling pathway promotes cell aging. Gene editing technology can be used to inhibit the expression of the mTOR gene, or edit its upstream regulatory factors, such as TSC1 and TSC2 genes. The TSC1/TSC2 complex can inhibit the mTOR signal, and modify it to enhance the inhibitory function, thereby reducing the activity of the mTOR signaling pathway. - **Example**: Targeted knockdown of the mTOR gene by CRISPR/Cas9 technology, or modification of the TSC1 and TSC2 genes, so that their expression products can more effectively inhibit the mTOR signal. This can reduce the overactivity of intracellular protein synthesis, energy metabolism and other processes, and slow down the rate of cell aging. For example, in mouse experiments, after inhibiting the mTOR signaling pathway by gene editing, the mouse's tissue and organ aging-related indicators such as the expression of cell aging markers and mitochondrial dysfunction were improved, and the lifespan was also extended. 2. **Activate the SIRT1 signaling pathway** - **Gene editing strategy**: SIRT1 is a deacetylase that depends on nicotinamide adenine dinucleotide (NAD+), which has the functions of regulating cell metabolism and delaying aging. The expression of SIRT1 gene can be upregulated by genetic engineering, or its interaction with upstream activating factors such as PGC-1α can be enhanced. PGC-1α can promote the activation of SIRT1, and it can be modified to make it bind more tightly to SIRT1 and have a stronger activation effect. - **Example**: Gene editing technology is used to optimize the promoter region of SIRT1 gene to make it easier to be transcriptionally activated, or directly overexpress the key domain that interacts with PGC-1α to enhance the activity of SIRT1 signaling pathway. In cell experiments, after activating the SIRT1 signaling pathway, the metabolic reprogramming in the cell develops in a direction that is more conducive to maintaining cell vitality, such as enhancing mitochondrial function and improving antioxidant defense capacity, thereby delaying cell aging. ### Regulating aging-related gene network 1. **Regulating p53 gene** - **Gene editing strategy**: p53 gene is an important tumor suppressor gene, and also plays a role in regulating cell aging. Wild-type p53 induces cell senescence when cells are subjected to stress such as DNA damage. Gene editing technology can be used to specifically mutate the p53 gene to change its function, such as reducing its activity in inducing cell senescence, or editing its downstream regulatory genes, such as the p21 gene. p21 is a downstream target gene of p53 that can inhibit cell cycle progression and lead to cell senescence.