AgeX Therapeutics, Inc., Alameda, CA 94501, USA.
Johns Hopkins University, Baltimore, MD 21218, USA.
Regen Med. 2019 Sep;14(9):867-886. doi: 10.2217/rme-2019-0062. Epub 2019 Aug 28.
Growing evidence supports the antagonistic pleiotropy theory of mammalian aging. Accordingly, changes in gene expression following the pluripotency transition, and subsequent transitions such as the embryonic-fetal transition, while providing tumor suppressive and antiviral survival benefits also result in a loss of regenerative potential leading to age-related fibrosis and degenerative diseases. However, reprogramming somatic cells to pluripotency demonstrates the possibility of restoring telomerase and embryonic regeneration pathways and thus reversing the age-related decline in regenerative capacity. A unified model of aging and loss of regenerative potential is emerging that may ultimately be translated into new therapeutic approaches for establishing induced tissue regeneration and modulation of the embryo-onco phenotype of cancer.
越来越多的证据支持哺乳动物衰老的拮抗多效性理论。因此，多能性转变后以及随后的转变（如胚胎-胎儿转变）导致的基因表达变化，虽然提供了肿瘤抑制和抗病毒生存益处，但也导致再生潜能丧失，从而导致与年龄相关的纤维化和退行性疾病。然而，将体细胞重编程为多能性证明了恢复端粒酶和胚胎再生途径的可能性，从而逆转与年龄相关的再生能力下降。衰老和再生潜能丧失的统一模型正在出现，这最终可能转化为建立诱导组织再生和调节癌症胚胎-癌表型的新治疗方法。
