Hallmarks of cancer and hallmarks of aging

Abstract

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.

Keywords: carcinogenesis; geroscience; hyperfunction theory; mTOR; oncology; rapamycin.

Figure 1

Hierarchical representation (from molecular to organismal levels) of the original hallmarks of cancer based on Hanahan and Weinberg. See text for explanation.

Figure 2

Hierarchical representation of the hallmarks of aging based on López-Otín et al. See text for explanation.

Figure 3

Hierarchical hallmarks of aging based on hyperfunction theory, applicable to humans. Non-life-limiting hallmarks are shown in brown color. See text for explanation.

Figure 4

Hierarchical hallmarks of aging based on hyperfunction theory, universal. Hyperfunction of intracellular signaling pathways leads to cellular and systemic hyperfunctions, which in turn lead to age-related diseases on the organismal level [56]. Specific hyperfunctions and diseases may be different in different species and therefore are not shown. For example, human systemic hyperfunctions (e.g., hypertension, hyperlipidemia, hyperglycemia) and diseases (e.g., cardio-vascular diseases) differ from diseases in C elegans [40, 41].