Age-associated decline of personal vitality is generally accepted as a congenital axiom. Increased susceptibility to disease with increasing age is likewise axiomatic. Hence, age-associated physical discompositions, such as DM, heart disease, cancer, and stroke, ranging in degree from asymptomatic to death, may be perceived as immutable and intrinsically human. Comorbidity increases with age (from ∼35% of patients over 65 to ∼70% of patients over 80), as does the cost of treating patients who present with comorbidity [
35]. In addition, comorbidity leads to an underreporting of deaths attributed to DM, as fatal events attributed to heart disease and stroke, for example, may not be ascribed to DM. Not surprisingly, decreased life expectancy of ∼4 years among individuals diagnosed with DM aged 65–74 was reported [
40]. The fact that all-cause mortality is three to four times greater in the DM population attests to its principal role in the lives of seniors. Not only does this amount to massive health care expenditures, but also represents a significant individual financial burden (direct and indirect costs totaling ∼132 billion US dollars or ∼111 billion euros in 2002 in the United States [
46]). It is predicted that by the year 2030 the number of individuals over 65 who suffer from DM will increase by 134%. The progressive nature of DM suggests that the more senior elderly demographic will suffer; between the years 2000 and 2050 the largest increase in DM prevalence is predicted to be among the elderly with the more represented senior demographic being above 75 years (271% increase in women and 437% increase in men) [
12]. The prevalence of DM in adults older than 60 years is estimated at ∼25% [
41].
Imperative to a full account of the impact of accumulating comorbid infirmities, in addition to recognizing the direct metabolic stress of DM, is accounting for the potential for a given intervention to affect the progress and manifestation of the disease. For example, aging is associated with a mortality-related decline in muscle strength [
80], a decline in muscle mass [
17], decreased oxygen consumption capacity (VO
2max), and a concomitant increase in fat mass [
86], along with increased disability [
10]. DM is coincidently related to increased adiposity [
5], decreased muscle mass [
94], and an elevated waist circumference (associated with both DM [
79] and metabolic syndrome [
59]). Curiously, DM is also associated with altered mitochondrial function relative to normal individuals, suggesting diminished VO
2max, and exercise capacity associated with DM may be related to a unique mitochondrial phenotype [
68]. Therefore, it is logical to propose that therapies aimed at reducing these age-related anthropomorphic and physiological changes (for example, via exercise intervention) may provide a stimulus, which is able to reverse or prevent age- and disuse-associated physiological changes and, thereby, reduce DM and its comorbidities. However, aging may also be inherently associated with progressive physiological changes, including those leading to an increased incidence of DM, which may remain unaffected by exercise (reviewed by Degens and Alway [
26] and Karakelides and Sreekumaran Nair [
58]). In light of the predictive statistics for DM and the economic and personal cost of the disease, it seems an intuitive responsibility to seek out etiologies and treatment for this sweeping threat.