Lifelong aerobic exercise protects against inflammaging and cancer

Abstract

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.

A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly

“…Specifically, low-to-moderate intensity exercise provides a hormetic stress stimulus that transiently activates evolutionary conserved cell danger response programs and, when repeated regularly, confers multi-systemic health benefits and protection against a spectrum of diseases [113], including respiratory tract infections and acute respiratory distress syndrome [114,115]. The preservation of SM function in old age is integral since contractile activity mobilizes leukocytes with high cytotoxicity and migratory potential (NK cells and CD8+ T lymphocytes), thus providing exchange between tissues and the circulatory system [116].…”

“…The preservation of SM function in old age is integral since contractile activity mobilizes leukocytes with high cytotoxicity and migratory potential (NK cells and CD8+ T lymphocytes), thus providing exchange between tissues and the circulatory system [116]. Over time, this process improves immunosurveillance and attenuates immunosenescence by preserving leukocyte function (T-cell, neutrophil, and NK cells), which lowers the immune response to bacterial challenge, enhances vaccination responses, and dampens systemic inflammation (inflammaging) [113,[116][117][118][119][120]. Currently, there is no scientific data regarding the specific benefits of physical activity on the risk of developing severe COVID-19 symptoms [112]; however, there is evidence that moderate intensity PA enhances protection against other viral infections such as influenza, rhinovirus, and herpes viruses [121,122].…”

Nutrition and exercise in Pompe disease

“…Concomitant accumulation of danger-associated molecular patterns (DAMPs), including oxidative damage, protein aggregates, and lipofuscin, is a common feature of biological aging, neurodegenerative disease, and lysosomal storage disorders (104)(105)(106)(107). Intervention strategies that rejuvenate the organelles/systems that regulate ATP and ROS production (mitochondria), waste recycling (autophagosome, lysosome, and 26 proteasome), and protein quality control (unfolded protein response, UPR ER and UPR MT ) may mitigate garbage buildup (e.g., 'autophagic blockage') and thereby preserve critical organ function (108). Exercise is an acute stress signal (ROS, Ca 2+ , pH, and hypoxia) that activates evolutionary conserved cell danger response programs (CDR and DDR, respectively), lowers the energy state of the cell (NAD + /NADH and AMP/ATP ratios), and promotes the release of neurotransmitters, hormones, and circulatory factors (e.g., exerkines), which coordinately stimulate mitochondrial biogenesis (CaMK II, PGC-1α, SIRT1, and AMPK), antioxidant defense (Nrf2-Keap1, NFκB, and MAPK), waste processing (ULK1-Beclin1, TFEB, and FOXO3a), and the immune response (NLRP3, IL-1β, IL-6, IL-10, IL-1ra, sTNF-R, and IL-18) (107-118).…”

Hematopoietic Stem and Progenitor Cell (HSPC) Mobilization Responses to Different Exercise Intensities in Young and Older Adults

“…Therefore, it stands to reason that elevated levels of this cytokine, at rest in OM, may serve to reduce the capacity for complete mobilization. The reality, however, is that many different cytokines are known to play a role in mobilization of HSPC, many of which appear to be altered by aging such as IL-6, IL-1β [24], and IGF-1 binding protein [5]. Age-related changes in any one of many different cytokines could alter the mobilization kinetics of HSPC.…”