BS2014: Exercising, Aging and Disease

Physical activity

muscular movement that increases energy expenditure

Physical inactivity

any decrease in body movement that produces decreased energy expenditure toward basal level

Exercise

planned, structured and repetitive physical activity designed to improve physical fitness

Physical fitness

how well one performs physical activity

Lifespan

duration of a person’s life

Healthspan

duration of a person’s life that they remain in excellent health

Health

physical, mental and social well-being

Sedentary behaviour

periods of low energy expenditure

Sedentary lifestyle relationship with mortality

• increased sitting time is correlated with higher mortality rate

• watching TV ≥ 6h/day → 2x higher mortality rate compared to <2h/day

• 30% higher mortality rate when sedentary people engage in high physical activity

SeDS (sedentary death syndrome)

deaths from non-communicable diseases attributed to physical inactivity

Obesity

chronic complex disease defined by excessive fat deposits that can impair health

Overweight

condition of excessive fat deposits

Global obesity prevalence

• 1 in 8 people in 2022

• from 1990 → 2022 — 2x more adults and 4x more adolescents are obese

Global overweight prevalence

43% of adults in 2022

Prevalence of obesity in UK

• 64% of population are overweight

• 26.2% of population are obese

Body weight homeostasis

increased food intake correlates with increased energy expenditure

Features of leptin

• produced primarily by white adipocytes

• bind to Ob-Rb receptors in hypothalamus

• Ob-Rb receptor activation leads to reduced food intake and increased energy expenditure (through adaptive thermogenesis)

Adaptative thermogenesis

decrease in energy expenditure

Leptin resistance in obesity

• failure for leptin to cross the blood-brain barrier

• impaired expresison of Ob-Rb receptors

• impaired leptin signalling pathway

Original causes of obesity

• overeating

• low energy expenditure

• physical inactivity

Energy “flipping point” in 1960-70 USA

the imbalance of food intake and physical activity caused by urbanisation and increased food supply containing refined carbs and fats

Fate of excess ingested foodstuffs

stored as lipids

Changes that occur with transition from normal physical activity to physical inactivity

• increased adipose mass

• increased cell volume

• increased FFA trafficking to triglyceride storage

• reduced turnover of adipose through lipolysis

• increased glucose uptake

Type 1 diabetes

autoimmune disease which destroys the insulin-producing β-cells of the pancreas

Type 2 diabetes

resistance to insulin produced by β-cells of Islets of Langerhans

Dysbiosis

imbalance of microbial communities within the body

Obesity in insulin resistance

• increased adipose cell mass

• dysbiosis

• leads to increased circulating FFAs which disrupt insulin receptor signalling

Effects of increased circulating FFA lead and insulin resistance

inhibition of:

• PI-3K signalling pathway

• insertion of GLUT-4 in plasma membrane

• inhibits GLUT-4 function

Reversing insulin resistance

reduced obesity → decreased FFAs → decreased insulin resistance → decreased stress of pancreatic β-cells

Atherosclerosis

chronic local inflammation developing in arteries due to the build-up of lipid deposits in plaques

Examples of anti-inflammatory cytokines

• TGF-β

• interleukins (10, 4)

Examples of pro-inflammatory cytokines

• IFN-γ

• TNFα

• interleukins (1,6,12,15,18)

Consensus estimates of how much 150 minutes of exercise per week can reduce risk of development of chronic diseases

• coronary heart disease — 40%

• high blood pressure — 50%

• stroke — 27%

• type 2 diabetes — 50%

• colon cancer — 20-50%

• Alzheimer’s disease — 33%

Benefits of trained muscle

• increases in muscle mass → reduced conversion of glucose to fat

• increased insulin sensitivity → reduced circulating FFAs

• ability to use lipid as an energy source → decreased fat storage

Benefits of improved physical fitness

• general improvement to health

• general improvement to wellbeing

• increased “brain health” and metabolic health

• resist the effects of pathogens, disease, and stress & helps recovery

Mechanisms allowing regular exercise to reduce chronic disease development?

• trained muscle

• improved physical fitness

• anti-inflammatory exerkines

• specific anti-tumour myokines

• acute activation of body stress responses

Benefits of improved anti-tumour myokines

reduces risk of developing at least 13 cancer types, and increases the survival rate of people with prostate, colorectal & breast cancer

Exerkines

hormones, metabolites, proteins and nucleic acids produced and released by different organ systems in response to exercise

Myokines

signalling proteins released by skeletal muscle fibres into the bloodstream during contraction

Autocrine effects of myokine IL-6

• acts on muscle to increase fatty oxidation

• increased glucose uptake

• increased muscle regeneration

Endocrine effects of myokine IL-6

• increases hepatic glucose production

• increases lipolysis to release FFAs for energy

• acts on intestinal L cells to increase GLP-1, which acts on the pancreas to increase insulin secretion

Endocrine effects of adipokine IL-6

acts on fatty liver to reduce insulin resistance and decrease inflammation

Fight-or-flight stress response

co-ordination of cardiovascular, musculoskeletal & nervous systems to extract oneself from the stimulus and restore body homeostasis

Consequence of chronic activation of stress

dysregulation of multiple body system leading to overall weakened stress responses and immune suppression

Consequences of chronic cortisol release

• increased appetite

• increased fat storage

• cortisol resistance (desensitisation of physiology stress response)

• weakened immune system

• repeated adrenaline surges → increased blood pressure → endothelial injury → increased risk of atherosclerosis

“Pleasure reward” hormones

• endocannabinoids

• endorphins

• dopamine

• serotonin

Sarcopenia

involuntary age-related loss of muscle mass and function

Hypoplasia

decrease in no. of muscle fibres

Atrophy

decrease in size of each muscle fibre

Neuropathic changes in sarcopenia

• loss of α-motor neurons in skeletal muscle → muscle denervation and reduced motor function

• loss of nerve innervation leads to denervation muscle atrophy

• axonal sprouting from remaining α-motor neurons: “protecting activity” → reduced fine control of motor unit recruitment when regulating force

Somatopause

progressive decrease in pituitary function to release growth factors leading to muscle atrophy

Myosteatosis

pathological infiltration of fat into the skeletal muscle, reducing muscle quality, strength and function

Consequences of myosteatosis

• increased load on specific skeletal muscles

• increased pro-inflammatory adipokines → promotes sarcopenia

• sarcopenia + obesity → increased FFA → increased myosteatosis

Primary treatment to limit sarcopenia

resistance training using weights or resistance bands

Aerobic fitness parameters

• VO2max

• exercise economy

• lactate-ventilatory threshold

• oxygen uptake kinetics