[1] 习近平：在科学家座谈会上的讲话[EB/OL]. [2020-09-11]. https://www.gov.cn/xinwen/2020-09/11/content_5542862.htm?eqid=e465fc63001ba5220000000264663d7d.
[2] 国务院办公厅关于发展银发经济增进老年人福祉的意见 [EB/OL]. [2020-09-11]. https://www.gov.cn/zhengce/content/202401/content_6926087.htm.
[3] Zhou Z, Liu Y T, Feng Y S, et al. Engineering longevitydesign of a synthetic gene oscillator to slow cellular aging [J]. Science, 2023, 380(6643): 376-381.
[4] Park S, Artan M, Han S H, et al. VRK-1 extends life span by activation of AMPK via phosphorylation[J]. Science Advances, 2020, 6(27): eaaw7824.
[5] Wang X Q, Jiang Q L, Zhang H D, et al. Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans[J]. Nature Communications, 2024, 15(1): 955.
[6] Yuan J, Chang S Y, Yin S G, et al. Two conserved epigenetic regulators prevent healthy ageing[J]. Nature, 2020, 579: 118-122.
[7] Lu T C, Brbić M, Park Y J, et al. Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution [J]. Science, 2023, 380(6650): eadg0934.
[8] Zhao Y Y, Xuan H W, Shen C, et al. Immunosuppression induced by brain-specific HDAC6 knockdown improves aging performance in Drosophila melanogaster[J]. Phenomics, 2022, 2(3): 194-200.
[9] Holtze S, Gorshkova E, Braude S, et al. Alternative animal models of aging research[J]. Frontiers in Molecular Biosciences, 2021, 8: 660959.
[10] Tabula Muris C. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse[J]. Nature, 2020, 583(7817): 590-595.
[11] Chen R P, Zhang K X, Chen H, et al. Telomerase deficiency causes alveolar stem cell senescence-associated low-grade inflammation in lungs[J]. The Journal of Biological Chemistry, 2015, 290(52): 30813-30829.
[12] Liu X, Jin Z G, Summers S, et al. Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior, and hypothalamic gene expression[J]. Cell Reports, 2022, 39(7): 110835.
[13] Zhang P Z, Catterson J H, Grönke S, et al. Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system[J]. Nature Aging, 2024, 4(4): 491-509.
[14] Yin P, Li S H, Li X J, et al. New pathogenic insights from large animal models of neurodegenerative diseases [J]. Protein & Cell, 2022, 13(10): 707-720.
[15] Colman R J, Anderson R M. Nonhuman primate calorie restriction[J]. Antioxidants & Redox Signaling, 2011, 14(2): 229-239.
[16] Jones R A, Harrison C, Eaton S L, et al. Cellular and molecular anatomy of the human neuromuscular junction [J]. Cell Reports, 2017, 21(9): 2348-2356.
[17] Zhang W Q, Wan H F, Feng G H, et al. SIRT6 deficiency results in developmental retardation in Cynomolgus monkeys[J]. Nature, 2018, 560(7720): 661-665.
[18] Wang F, Zhang W Q, Yang Q Y, et al. Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing[J]. Protein & Cell, 2020, 11(11): 809-824.
[19] Liang C Q, Ke Q, Liu Z P, et al. BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in Primates[J]. Nucleic Acids Research, 2022, 50(6): 3323-3347.
[20] Yang W L, Guo X Y, Tu Z C, et al. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis[J]. Protein & Cell, 2022, 13(1): 26-46.
[21] Liu Z, Li X, Zhang J T, et al. Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2[J]. Nature, 2016, 530(7588): 98-102.
[22] Qiu P Y, Jiang J, Liu Z, et al. BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders[J]. National Science Review, 2019, 6(1): 87-100.
[23] Liu Z, Cai Y J, Wang Y, et al. Cloning of macaque monkeys by somatic cell nuclear transfer[J]. Cell, 2018, 172(4): 881-887.e7.
[24] Wu S H, Li X, Qin D D, et al. Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/ Cas9-based gene editing in the brain of adolescent Rhesus monkeys[J]. Science Bulletin, 2021, 66(9): 937-946.
[25] Chen Y C, Yu J H, Niu Y Y, et al. Modeling rett syndrome using TALEN-edited MECP2 mutant Cynomolgus monkeys[J]. Cell, 2017, 169(5): 945-955.e10.
[26] Kubben N, Zhang W Q, Wang L X, et al. Repression of the antioxidant NRF2 pathway in premature aging[J]. Cell, 2016, 165(6): 1361-1374.
[27] Zhang W, Li J, Suzuki K, et al. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging[J]. Science, 2015, 348(6239): 1160-1163.
[28] Liu G H, Suzuki K, Li M, et al. Modelling Fanconi Anemia pathogenesis and therapeutics using integrationfree patient-derived iPSCs[J]. Nature Communications, 2014, 5: 4330.
[29] Yan P Z, Li Q Q, Wang L X, et al. FOXO3-Engineered human ESC-derived vascular cells promote vascular protection and regeneration[J]. Cell Stem Cell, 2019, 24(3): 447-461.e8.
[30] López-Otín C, Blasco M A, Partridge L, et al. Hallmarks of aging: An expanding universe[J]. Cell, 2023, 186(2): 243-278.
[31] Liu Z P, Ji Q Z, Ren J, et al. Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging[J]. Developmental Cell, 2022, 57(11): 1347-1368.e12.
[32] Zhao H K, Ji Q Z, Wu Z M, et al. Destabilizing heterochromatin by APOE mediates senescence[J]. Nature Aging, 2022, 2(4): 303-316.
[33] Liu X Q, Liu Z P, Wu Z M, et al. Resurrection of endogenous retroviruses during aging reinforces senescence[J]. Cell, 2023, 186(2): 287-304.e26.
[34] Zhang H, Li J M, Yu Y, et al. Nuclear Lamina erosioninduced resurrection of endogenous retroviruses underlies neuronal aging[J]. Cell Reports, 2023, 42(11): 113396.
[35] Yang J H, Hayano M, Griffin P T, et al. Loss of epigenetic information as a cause of mammalian aging[J]. Cell, 2023, 186(2): 305-326.e27.
[36] Bleve A, Motta F, Durante B, et al. Immunosenescence, inflammaging, and frailty: Role of myeloid cells in agerelated diseases[J]. Clinical Reviews in Allergy & Immunology, 2023, 64(2): 123-144.
[37] Franceschi C, Garagnani P, Parini P, et al. Inflammaging: A new immune-metabolic viewpoint for age-related diseases[J]. Nature Reviews Endocrinology, 2018, 14(10): 576-590.
[38] Mittelbrunn M, Kroemer G. Hallmarks of T cell aging[J]. Nature Immunology, 2021, 22(6): 687-698.
[39] Brauning A, Rae M, Zhu G, et al. Aging of the immune system: Focus on natural killer cells phenotype and functions[J]. Cells, 2022, 11(6): 1017.
[40] Li X, Li C T, Zhang W Y, et al. Inflammation and aging: Signaling pathways and intervention therapies[J]. Signal Transduction and Targeted Therapy, 2023, 8(1): 239.
[41] Xu D C, Jin T J, Zhu H, et al. TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging[J]. Cell, 2018, 174(6): 1477-1491.e19.
[42] Bao W D, Pang P, Zhou X T, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease[J]. Cell Death and Differentiation, 2021, 28(5): 1548-1562.
[43] Yi W W, Zhang J H, Huang Y X, et al. Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells[J]. Leukemia, 2024, 38(5): 1003-1018.
[44] Li X, Wang J Q, Wang L Y, et al. Lipid metabolism dysfunction induced by age-dependent DNA methylation accelerates aging[J]. Signal Transduction and Targeted Therapy, 2022, 7(1): 162.
[45] Li Z C, Xu K, Zhao S, et al. SPATA4 improves aging-induced metabolic dysfunction through promotion of preadipocyte differentiation and adipose tissue expansion[J]. Aging Cell, 2021, 20(1): e13282.
[46] Dou X F, Fu Q, Long Q L, et al. PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy[J]. Nature Metabolism, 2023, 5(11): 1887-1910.
[47] Wang S, Zheng Y X, Li J Y, et al. Single-cell transcriptomic atlas of primate ovarian aging[J]. Cell, 2020, 180(3): 585-600.e19.
[48] Zhang W Q, Zhang S, Yan P Z, et al. A single-cell transcriptomic landscape of primate arterial aging[J]. Nature Communications, 2020, 11(1): 2202.
[49] Sun S H, Li J M, Wang S, et al. CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord [J]. Nature, 2023, 624(7992): 611-620.
[50] Li J Y, Zheng Y X, Yan P Z, et al. A single-cell transcriptomic atlas of primate pancreatic islet aging[J]. National Science Review, 2021, 8(2): nwaa127.
[51] Ke H N, Tang S Y, Guo T, et al. Landscape of pathogenic mutations in premature ovarian insufficiency[J]. Nature Medicine, 2023, 29(2): 483-492.
[52] Oh H S H, Rutledge J, Nachun D, et al. Organ aging signatures in the plasma proteome track health and disease [J]. Nature, 2023, 624(7990): 164-172.
[53] Li J M, Xiong M Z, Fu X H, et al. Determining a multimodal aging clock in a cohort of Chinese women[J]. Med, 2023, 4(11): 825-848.e13.
[54] Zheng Z K, Li J M, Liu T Z, et al. DNA methylation clocks for estimating biological age in Chinese cohorts [J]. Protein & Cell, 2024, 15(8): 575-593.
[55] Xia X, Chen X W, Wu G, et al. Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle[J]. Nature Metabolism, 2020, 2(9): 946-957.
[56] Consortium A B, Suo J L, Gan Y B, et al. A framework of biomarkers for skeletal aging: A consensus statement by the aging biomarker consortium[J]. Life Medicine, 2023, 2(6): lnad045.
[57] Consortium A B, Zhang W W, Che Y, et al. A biomarker framework for cardiac aging: The aging biomarker consortium consensus statement[J]. Life Medicine, 2023, 2(5): lnad035.
[58] Consortium A B, Jiang M M, Zheng Z Z, et al. A biomarker framework for liver aging: The aging biomarker consortium consensus statement[J]. Life Medicine, 2024, 3(1): lnae004.
[59] Ren J, Song M S, Zhang W Q, et al. The Aging Biomarker Consortium represents a new era for aging research in China[J]. Nature Medicine, 2023, 29(9): 2162-2165.
[60] Guo Y, You J, Zhang Y, et al. Plasma proteomic profiles predict future dementia in healthy adults[J]. Nature Aging, 2024, 4(2): 247-260.
[61] Shen Y, Wang H B, Sun Q Y, et al. Increased plasma beta-secretase 1 may predict conversion to Alzheimer’s disease dementia in individuals with mild cognitive impairment[J]. Biological Psychiatry, 2018, 83(5): 447-455.
[62] Jia J P, Ning Y Y, Chen M L, et al. Biomarker changes during 20 years preceding Alzheimer’s disease[J]. The New England Journal of Medicine, 2024, 390(8): 712-722.
[63] Xiang J, Tao Y Q, Xia Y Y, et al. Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies[J]. Cell, 2023, 186(16): 3350-3367.e19.
[64] Li Y Y, Ying Y Q, Yao T Y, et al. Decreased water exchange rate across blood–brain barrier in hereditary cerebral small vessel disease[J]. Brain, 2023, 146(7): 3079-3087.
[65] Hamczyk M R, Nevado R M, Barettino A, et al. Biological versus chronological aging: JACC focus seminar[J]. Journal of the American College of Cardiology, 2020, 75(8): 919-930.
[66] Covarrubias A J, Perrone R, Grozio A, et al. NAD(+) metabolism and its roles in cellular processes during ageing [J]. Nature Reviews Molecular Cell Biology, 2021, 22(2): 119-141.
[67] Strong R, Miller R A, Bogue M, et al. Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects[J]. Aging Cell, 2020, 19(11): e13269.
[68] Shan H Z, Geng L L, Jiang X Y, et al. Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells[J]. Protein & Cell, 2022, 13(7): 532-539.
[69] Yang Y, Lu X, Liu N, et al. Metformin decelerates aging clock in male monkeys[J]. Cell, 2024, 187(22): 6358-6378.
[70] Novais E J, Tran V A, Johnston S N, et al. Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice[J]. Nature Communications, 2021, 12(1): 5213.
[71] Zhang P S, Kishimoto Y, Grammatikakis I, et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model[J]. Nature Neuroscience, 2019, 22(5): 719-728.
[72] Syed D N, Adhami V M, Khan M I, et al. Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin[J]. Anti-Cancer Agents in Medicinal Chemistry, 2013, 13(7): 995-1001.
[73] Grynkiewicz G, Demchuk O M. New perspectives for fisetin[J]. Frontiers in Chemistry, 2019, 7: 697.
[74] Davidsohn N, Pezone M, Vernet A, et al. A single combination gene therapy treats multiple age-related diseases [J]. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(47): 23505-23511.
[75] Lu Y C, Brommer B, Tian X, et al. Reprogramming to recover youthful epigenetic information and restore vision [J]. Nature, 2020, 588(7836): 124-129.
[76] Hishida T, Yamamoto M, Hishida-Nozaki Y, et al. In vivo partial cellular reprogramming enhances liver plasticity and regeneration[J]. Cell Reports, 2022, 39(4): 110730.
[77] Jing Y B, Jiang X Y, Ji Q Z, et al. Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation[J]. Cell Stem Cell, 2023, 30(11): 1452-1471.e10.
[78] Deng L P, Ren R T, Liu Z P, et al. Stabilizing heterochromatin by DGCR8 alleviates senescence and osteoarthritis[J]. Nature Communications, 2019, 10(1): 3329.
[79] Liang C Q, Liu Z P, Song M S, et al. Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration[J]. Cell Research, 2021, 31(2): 187-205.
[80] Ye Y X, Yang K, Liu H S, et al. SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B[J]. Nature Aging, 2023, 3(10): 1269-1287.
[81] Sun S M, Qin W F, Tang X L, et al. Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model[J]. Science Advances, 2020, 6(8): eaay5556.
[82] Wang W, Zheng Y X, Sun S H, et al. A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence[J]. Science Translational Medicine, 2021, 13(575): eabd2655.
[83] Ma S, Ji Z, Zhang B, et al. Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging[J/OL]. Cell, [2024-11-04]. https://www.cell.com/cell/abstract/S0092-8674(24)01201-7.
[84] Golpanian S, DiFede D L, Khan A, et al. Allogeneic human mesenchymal stem cell infusions for aging frailty[J]. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences, 2017, 72(11): 1505-1512.
[85] Lee W S, Kim H J, Kim K I, et al. Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: A phase IIb, randomized, placebo-controlled clinical trial [J]. Stem Cells Translational Medicine, 2019, 8(6): 504-511.
[86] Sun S M, Meng Y, Li M Y, et al. CD133+ endotheliallike stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice[J]. Nature Aging, 2023, 3(11): 1401-1414.
[87] Amor C, Feucht J, Leibold J, et al. Senolytic CAR T cells reverse senescence-associated pathologies[J]. Nature, 2020, 583(7814): 127-132.
[88] Amor C, Fernández-Maestre I, Chowdhury S, et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction[J]. Research Square, 2023: rs.3.rs-rs.3385749.
[89] Yang D, Sun B, Li S R, et al. NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman Primates[J]. Science Translational Medicine, 2023, 15(709): eadd1951.
[90] Wang T W, Johmura Y, Suzuki N, et al. Blocking PDL1-PD-1 improves senescence surveillance and ageing phenotypes[J]. Nature, 2022, 611(7935): 358-364.
[91] Waziry R, Ryan C P, Corcoran D L, et al. Effect of longterm caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial[J]. Nature Aging, 2023, 3: 248-257.
[92] Rhoads T W, Anderson R M. Caloric restriction has a new player[J]. Science, 2022, 375(6581): 620-621.
[93] Sun S H, Ma S, Cai Y S, et al. A single-cell transcriptomic atlas of exercise-induced anti-inflammatory and geroprotective effects across the body[J]. Innovation (Cambridge (Mass)), 2023, 4(1): 100380.
