6 6. Experience-Dependent Modulation of Aging: A Role for Epigenetics? The experience-dependent nature of aging has important implications for the research questions that are posed (e.g., How do speciﬁc events/factors at diﬀerent life stages interact to modulate the rate of aging?). This suggests that cumulative prenatal, earlylife, young adulthood, and later life circumstances impact pathways to aging. This could be mediated in part by alterations in the stress system across the life course: induced alterations in neurological substrates that signal stressful information [114, 115] as well as neurobio- logical and allostatic processes involving inﬂammation and oxidative stress [72, 116]. Thus, as suggested by Epel [72], psychological and metabolic stress may constitute a potent recipe for accelerated cellular aging. Epigenetics, which involves the laying of relatively stable imprints on the genome that impact gene expression and cellular function over time [117, 118], is increasingly revealed as a candidate intersection point between biological and psychosocial processes in several age-related chronic diseases [119, 120]. It is known that epigenetic marks are altered in aging [121, 122] and in several age-related disease states such as cancer, neurodegenerative, and autoimmune diseases [123], as well as type 2 diabetes [124, 125]. The altered epigenome could therefore mediate the experience- dependent modulation of the aging rate and age-related morbidities across the life span. Further to that point, mito- chondria themselves possess a plastic mtDNA epigenome [126] and have the potential to generate powerful signals capable of aﬀecting the nuclear epigenome [127, 128], making these organelles well equipped to play a critical interfacing role between the environment and the genome [127]. Although this remains to be empirically supported, it is an hypothesis that integrates knowledge about the health consequences attributable to genetic variations, calo- rie intake, physical activity/inactivity, and neurobiological substrates of psychosocial stress into a uniﬁed framework for aging research. Taken together, the reviewed literature indicates that an increasing number of biological factors (e.g., mtDNA hap- lotypes, hormones, genetic polymorphisms aﬀecting cellular signalling pathways, factors epigenetic imprints), behavioral and (e.g., diet/calorie intake, and exercise), and psychoso- cial (e.g., psychological stress, depression, personality, and marital status) factors inﬂuence the aging process. The challenge lying ahead of researchers in this ﬁeld lies in the exploration of the intersection points linking these multiple levels of analysis spanning several disciplines. For example, what physiological processes interact with the psychosocial eﬀects of being married, of meditating regularly, or of experiencing psychological well-being and sense of purpose in life, which ultimately culminate in reduced telomere shortening [129]? What combination of elements lead to resilience and successful adaptation to aging? And what are the combinations leading to age-related risk and ill- health? Interdisciplinary initiatives aimed at describing the interactive biopsychosocial processes that link these multiple levels will yield new knowledge of the pathways to aging, Journal of Aging Research which in turn will inform eﬀective prevention and interven- tion strategies. Network perspectives inspired from systems biology [130, 131] allowing modeling of complex nonlinear interactions among the studied variables may prove useful in this endeavour. Similarly, building comprehensive theories of aging will require the combined eﬀorts of researchers from diﬀerent disciplines contributing diverse complementary expertise, perspectives, and approaches to study aging. 7. Individualized Aging Trajectories Eﬀective strategies for promoting healthy aging will need to be individualized. The perfect individualization of treatment and prevention of age-related disorders may appear as an unattainable utopia at this point in time. This is particularly the case because up until now, our knowledge of the dynamic interplay between the diﬀerent biological and psychosocial levels of analysis is still fragmentary, which impedes discoveries about the complex processes from which individual-speciﬁc pathways of aging emerge. A well-known principle in biology and developmental psychopathology is that of “equiﬁnality,” whereby multiple distinct pathways lead to the same outcome. The reciprocal principle is that of “multiﬁnality,” whereby the same set of pathways lead to diﬀerent outcomes [112]. Likewise, the source of interindividual diﬀerences in aging trajectories undoubtedly lies in the interplay of several interdependent pathways of which there is no single universal “right” combination that can be prescribed. Means must be developed to distinguish between optimal (i.e., living to your full biological potential) and suboptimal (i.e., dying or having disease sooner than your constitution should permit) rates/trajectories of aging. From the onset, it can be established that optimal aging is characterized by a slow progressive decline in physiological functions, maintenance of well-being for the majority of the lifespan, and only a short period of very poor physical health leading to death. But what are the biomolecular (i.e., gene expression, mitochondrial function, and biomarkers) sings of optimal adaptation to the passing decades? What are the normative ontogenic trajectories, or healthy biological and physiological signatures of successful aging? Having answers to these questions will enable researchers to more accurately distinguish dysfunction from normal function in diﬀerent aged organ systems. Ryﬀ, Singer and colleagues have established biological correlates and a conceptual frame- work aimed at deciphering the biological and psychosocial underpinnings of resilience, positive health, and successful aging [71, 132–134]. Building such a knowledge base of normal molecular, cellular, physiological, and psychosocial signatures of aging may also translate into more reﬁned means to detect predisease or preclinical deviations from normal adaptation and to prevent age-related diseases. Thus far, despite the fact that more resources are being invested to study speciﬁc aspects of the normal pathways leading to healthy aging [71, 132–134], relatively little data is available to address pressing questions about healthy aging. A noteworthy exception is the MacArthur Studies of Successful