Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Aging (Albany NY). 2022 May 9;14(9):4176-4187. doi: 10.18632/aging.204082.
A thought-provoking article by Gems and de Magalhães suggests that canonic hallmarks of aging are superficial imitations of hallmarks of cancer. I took their work a step further and proposed hallmarks of aging based on a hierarchical principle and the hyperfunction theory.To do this, I first reexamine the hallmarks of cancer proposed by Hanahan and Weinberg in 2000. Although six hallmarks of cancer are genuine, they are not hierarchically arranged, i.e., molecular, intra-cellular, cellular, tissue, organismal and extra-organismal. (For example, invasion and angiogenesis are manifestations of molecular alterations on the tissue level; metastasis on the organismal level, whereas cell immortality is observed outside the host).The same hierarchical approach is applicable to aging. Unlike cancer, however, aging is not a molecular disease. The lowest level of its origin is normal intracellular signaling pathways such as mTOR that drive developmental growth and, later in life, become hyperfunctional, causing age-related diseases, whose sum is aging. The key hallmark of organismal aging, from worms to humans, are age-related diseases. In addition, hallmarks of aging can be arranged as a timeline, wherein initial hyperfunction is followed by dysfunction, organ damage and functional decline.
一篇发人深省的文章，由 Gems 和 de Magalhães 撰写，提出衰老的典型特征是对癌症典型特征的表面模仿。我进一步根据层次原则和超功能理论，提出了基于衰老的典型特征。为此，我首先重新审视了 Hanahan 和 Weinberg 于 2000 年提出的癌症典型特征。虽然癌症的六个典型特征是真实存在的，但它们并不是按照层次排列的，即分子、细胞内、细胞、组织、机体和机体外。（例如，侵袭和血管生成是组织水平上分子改变的表现；转移是在机体水平上，而细胞永生化则发生在宿主之外）。同样的层次方法适用于衰老。然而，与癌症不同，衰老不是一种分子疾病。其起源的最低层次是正常的细胞内信号通路，如 mTOR，它驱动着发育生长，而在生命后期变得超功能，导致与年龄相关的疾病，这些疾病的总和就是衰老。从蠕虫到人，机体衰老的关键典型特征是与年龄相关的疾病。此外，衰老的典型特征可以按照时间线排列，其中初始的超功能之后是功能障碍、器官损伤和功能下降。
