From the Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, CA (E.B., P.M.R., A.P.L., J.C.I.B.); and Universidad Católica San Antonio de Murcia, Guadalupe, Spain (P.M.R.).
Circ Res. 2018 Jan 5;122(1):128-141. doi: 10.1161/CIRCRESAHA.117.311866.
All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging. Therefore, modalities that reinforce regeneration can antagonize aging. Recent advances in the field of regenerative medicine have shown that aging is not an irreversible process. Conversion of somatic cells to embryonic-like pluripotent cells demonstrated that the differentiated state and age of a cell is not fixed. Identification of the pluripotency-inducing factors subsequently ignited the idea that cellular features can be reprogrammed by defined factors that specify the desired outcome. The last decade consequently has witnessed a plethora of studies that modify cellular features including the hallmarks of aging in addition to cellular function and identity in a variety of cell types in vitro. Recently, some of these reprogramming strategies have been directly used in animal models in pursuit of rejuvenation and cell replacement. Here, we review these in vivo reprogramming efforts and discuss their potential use to extend the longevity by complementing or augmenting the regenerative capacity.
所有生物在个体发育后都会经历全身性的生理衰退，这一过程被称为衰老。现代医学延长了人类的预期寿命，但这也导致了老龄化社会的出现，使更多人易患退行性疾病。因此，需要寻找新的干预措施，使健康寿命与寿命同步延长。生物的再生能力维持着它们的生物完整性，因此是对抗衰老的主要手段。然而，哺乳动物的再生能力较低，并且在衰老过程中进一步下降。因此，增强再生能力的方法可以对抗衰老。再生医学领域的最新进展表明，衰老是一个可以逆转的过程。体细胞向胚胎样多能细胞的转化表明，细胞的分化状态和年龄并不是固定的。随后发现的多能性诱导因子激发了这样一种想法，即通过定义的因子可以重编程细胞的特征，从而达到预期的结果。因此，在过去的十年中，人们进行了大量的研究，这些研究改变了细胞的特征，包括衰老的标志性特征，以及体外各种细胞类型的细胞功能和特性。最近，这些重编程策略中的一些已被直接应用于动物模型，以追求年轻化和细胞替代。在这里，我们回顾了这些体内重编程的努力，并讨论了它们通过补充或增强再生能力来延长寿命的潜在用途。
