Core Viewpoint - The research published in PNAS reveals that brain aging follows a nonlinear process rather than a linear one, with insulin resistance being a key factor influencing this aging process [1][6][12]. Group 1: Nonlinear Aging Process - The study analyzed fMRI data from over 19,300 participants, showing that brain network instability changes with age in a nonlinear (S-shaped) manner [6][7]. - The S-shaped model indicates a slow change in early life, followed by accelerated changes approaching middle age (around 43.7 years), and then a plateau phase [9][11]. - Insulin resistance is identified as a driving mechanism for the trajectory of brain aging, affecting glucose metabolism and neuronal energy supply [12][17]. Group 2: Role of Ketone Bodies - Ketone bodies, such as D-β-hydroxybutyrate (D-βHB), can bypass insulin resistance and provide an alternative energy source for neurons, making them a potential intervention for brain aging [19][18]. - A study involving 101 healthy adults demonstrated that D-βHB significantly stabilizes brain networks, especially in the 40-59 age group, where the effect is 84.62% greater than in the 20-39 age group [24][26]. - The effectiveness of D-βHB diminishes in the 60-79 age group, indicating that middle age (40-59 years) is a critical intervention period for brain health [25][26].

Core Viewpoint - The research published in PNAS reveals that brain aging follows a nonlinear process rather than a linear one, with insulin resistance being a key factor influencing this aging process [1][6][12]. Group 1: Nonlinear Aging Process - The study analyzed fMRI data from over 19,300 participants, demonstrating that brain network instability changes with age in a nonlinear (S-shaped) manner [6][7]. - The S-shaped model indicates a slow change in early life, followed by accelerated changes approaching middle age (around 43.7 years), and then a plateau phase [9][11]. - Insulin resistance is identified as a driving mechanism for the trajectory of brain aging, affecting glucose metabolism and neuronal energy supply [12][17]. Group 2: Role of Ketone Bodies - Ketone bodies, such as D-β-hydroxybutyrate (D-βHB), can bypass insulin resistance and provide an alternative energy source for neurons, making them a potential intervention for combating brain aging [19][18]. - A study involving 101 healthy adults showed that D-βHB significantly stabilizes brain networks, particularly in the 40-59 age group, where the effect is 84.62% greater than in the 20-39 age group [24][26]. - The effectiveness of D-βHB diminishes in the 60-79 age group, indicating that middle age (40-59 years) is a critical intervention period for brain health [25][26].