Date Published: January 25, 2019
Publisher: Public Library of Science
Author(s): Mats I. Nilsson, Jacqueline M. Bourgeois, Joshua P. Nederveen, Marlon R. Leite, Bart P. Hettinga, Adam L. Bujak, Linda May, Ethan Lin, Michael Crozier, Daniel R. Rusiecki, Chris Moffatt, Paul Azzopardi, Jacob Young, Yifan Yang, Jenny Nguyen, Ethan Adler, Lucy Lan, Mark A. Tarnopolsky, Antonio Musaro.
Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation (‘inflammaging’), which predispose for a wide spectrum of chronic diseases, including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the ‘physiologic reserve’ of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice.
In the aftermath of the sociopolitical, scientific, and medical advances of the 20th century, global fertility and mortality rates have steadily declined and average life-expectancies risen [1–3]. Albeit a remarkable human achievement per se, population demographics are also shifting in favor of older adults (≥60 y), and this group is expected to increase from 800 million to 2 billion in the next four decades, representing 22% of the total world population by 2050 . Age-related disorders currently account for ≈25% of the global burden of disease with the leading contributors being the chronic, non-communicable diseases (NCDs), such as cardiovascular disease (CVD), cancer, musculoskeletal disorders (MSD), and mental/neurological conditions . Because population aging is expected to impose a formidable challenge in terms of escalating health-care costs, and NCDs are the principal preventable cause of death and disability, a greater emphasis must be put on preventive medicine in the 21st century .
Cumulative evidence over the last 50 years unequivocally shows that sedentary living accelerates organ deterioration and increases all-cause mortality risk. In contrast, aerobic exercise training promotes healthy aging and extends average life expectancy by 3–10% . Our data confirm that lifelong running provides significant health benefits and protects against cancer, while only modestly improving the median lifespan of naturally-aged mice. For more substantial pro-longevity benefits ‘of mice and men’, a combination of lifestyle modification, rejuvenation biotechnology, and intermittent pharmacotherapy may be necessary (e.g., anti-aging polytherapy). Given that the global burden of chronic disease is steadily rising (population aging and physical inactivity pandemic), the development of innovative strategies to increase daily PA levels at the societal level, and/or alternative means to harness the multi-systemic benefits of exercise (e.g., exercise mimetics), will be of paramount importance in the 21st century.