Aging has traditionally been viewed as a multifaceted process influenced by various factors, including genetics, environment, and lifestyle, all interconnected with lifespan and age-related diseases (Fontana, Kennedy, Longo, Seals, & Melov, 2014; Kenyon, 2010). The intricacies of aging have given rise to numerous theories, numbering in the hundreds, yet consensus remains elusive (Medvedev, 1990). Recently, the concept of the “hallmarks of aging” has emerged to elucidate the underlying principles of aging, encompassing a network of interconnected molecular and cellular processes (Blackburn & Epel, 2012; Franceschi, Garagnani, Parini, Giuliani, & Santoro, 2018; Kennedy et al., 2014; Lopez-Otin, Blasco, Partridge, Serrano and Kroemer, 2013, Lopez-Otin, Blasco, Partridge, Serrano and Kroemer, 2023; Riera & Dillin, 2015).

In recent times, groundbreaking discoveries have transformed the landscape of biological aging, rekindling humanity's longstanding aspiration to conquer the aging process. Technologies such as pluripotent stem cell induction and somatic cell nuclear transfer have introduced innovative avenues for reversing aging through artificial manipulation (Czernik, Anzalone, Palazzese, Oikawa, & Loi, 2019; Gurdon, 1962; Mizutani, Ono, Li, Maki-Suetsugu, & Wakayama, 2008; Ocampo et al., 2016; Takahashi & Yamanaka, 2006; Yagi et al., 2012). The application of parabiosis technology has spurred investigations into systemic factors capable of rejuvenating old organisms into a more youthful state (Ashapkin, Kutueva, & Vanyushin, 2020; I. M. Conboy et al., 2005; M. J. Conboy, Conboy, & Rando, 2013). Furthermore, selective methods for eliminating senescent cells have illuminated the technical potential for restoring youthful vitality (Kirkland & Tchkonia, 2020; M. Xu et al., 2018). These recent breakthroughs have challenged traditional notions of aging as irreversible and inevitable, opening up new possibilities for achieving ultimate control over the aging process. Consequently, these advancements in aging intervention demand a fresh perspective on aging within a completely different framework.

As a solution to this, a novel approach seeks to elucidate and regulate the aging process through the lens of biological responsiveness, defined as the ability of an organism to respond to changes in its internal and external environment (Betts et al., 2022), which is operated under physiological and behavioral mechanism (described in chapter 2). This review delves into the age-dependent alterations in responsiveness as the fundamental mechanism of aging and explores its potential modulation for intervening in the aging process and addressing age-related disorders.