M3 Aging, Physical, and Physiological Function

Ulukhaktok community

study by Collings 2001 looked at how Ulukhaktok elders viewed aging

• Elders considered >50 yrs

• highly valued in society

  • providers of hunted food

  • exemplars of an idealized, traditional lifestyle

  • nexus of social relations

Ulukhaktok community themes

4 themes arose from the Collings 2001 study

• Natural

• Domestic

• Economic

• Attitudinal

attitudinal components of successful aging

mental state, alcohol, respect, wisdom, sociality

results

components of successful aging (natural, domestic, economic, attitudinal)

• when genders were combined (sorted by age)

  • same general responses (attitudinal most impt)

• when ages were combined (sorted by gender) 

  • differences emerged

  • attitudinal was #1 priority for males and females

  • second most: males prioritized economic and females prioritized natural

attitudinal components of successful aging

• when genders were combined (sorted by age)

  • both older and younger ages prioritized wisdom

• when ages were combined (sorted by gender) differences emerged

  • males prioritized mental state while females prioritized wisdom

Ulukhaktok aging

individual’s attitudes during late life, particularly their willingness to act as a transmitter of knowledge is a major determinant of successful aging

• health issues are important but it is though that declining health is natural and inevitable

• attitudes towards aging is most important

how to think about successful aging

recognize diversity in older adults

recognize diversity in perceptions of successful/healthy aging among older adults

listen to older adults with whom you are working and consider environmental, sociocultural, and individual contexts

physiological reserve

extra capacity the body has to respond to stress, illness, or injury beyond what is needed for normal daily function

• e.g. a healthy heart can inc cardiac output during exercise or illnesss

homeostenosis

the narrowing of the body’s ability to maintain homeostasis as people age

• in other words, the physiological “buffer” that helps your body respond to stressors becomes smaller over time

aging and physiological reserves

as people age, they use more and more of there physiological reserves for daily use

• when no more physiological reserves are available, an individual can go beyond the precipice

precipice

the precipice can represent any threshold

• could be anything

  • death

  • debilitating injury

  • independent living can no longer continue

cardiac aging

several things happen to the heart as you age

1. structural changes

2. functional changes

3. cellular/extracellular changes

4. overall consequences

structural changes

• Left ventricle (LV):

  • Wall thickens (hypertrophy of remaining myocytes)

  • Chamber volume decreases → less filling capacity

    • Increased epicardial fat

• Atria:

  • Atrial remodeling → increased atrial volume

  • Consequence: higher risk of atrial fibrillation

• Heart valves:

  • Aortic valve calcification increases with age → stiffening → contributes to heart failure

  • All valves → increased thickness, circumference, luminal surface area

    • Results in fluid pooling in lungs, abdomen, legs, feet

functional changes

• Diastolic function declines

  • Partly due to slowed Ca²⁺ removal from cardiomyocytes → delayed relaxation

• Pacemaker (SA node) changes

  • Fewer ion channels

  • Reduced responsiveness to sympathetic stimulation → slower heart rate increases under stress

cellular/extracellular changes

• Ventricular myocytes:

  • Loss of myocytes with age

  • Remaining myocytes hypertrophy to compensate (males moreso than females)

• Epicardial tissue:

  • Increased epicardial adipose tissue

  • Increased fibroblasts → more fibrosis → stiffer heart

overall consequences

• Stiffer ventricles → impaired diastolic filling

• Higher atrial pressures → atrial dilation → risk of arrhythmias

• Reduced ability to increase heart rate and cardiac output during stress

• Increased susceptibility to heart failure with preserved ejection fraction

early to late diastolic filling ratio

atrial to ventricle blood flow decreases with age

• reduced diastolic function

Jakovlgevic DJ et al. 2015

peak cardiac power output

heart’s pumping ability decreases with age

Jakovlgevic DJ et al. 2015

PCr to ATP ratio

the amount of ATP that 1 PCr molecule makes

• generally decreases with age but shown to be maintained with regular PA (walking 10,000+ steps per day)

Jakovlgevic DJ et al. 2015

peak O2 consumption

highest rate at which an individual can consume oxygen during maximal or near-maximal exercise (VO₂) peak

• generally decreases with age but effects shown to be diminished with regular PA (walking 10,000+ steps per day)

Jakovlgevic DJ et al. 2015

vascular aging

several things happens to your blood vessels as you age

1. endothelial dysfunction

2. blood pressure changes

endothelial dysfunction

reduced ability of the endothelium to mediate vasodilation, regulate blood flow, and maintain vascular health

• postmenopausal women show greater endothelial dysfunction than age-matched men

blood pressure changes

systolic pressure increases with age → hypertension increase

• Aortic stiffening → less elastic recoil

• Peripheral vascular resistance may increase due to remodeling and reduced vasodilatory capacity

forced expiratory volume and age

FEV is reduced with age

• males start slightly higher than females on their regression line

Amara et al. 2001

FFM and FEV

men and women with greater FFM (fat free mass, more metabolically active tissue) had greater FEV

Amara et al. 2001

grip strength and FEV

men and women with greater grip strength had greater FEV

Amara et al. 2001

lung function and aging

1. decreased elastic recoil

2. decrease in chest wall compliance

3. decrease in maximal expiratory flow volume

4. airway closure at higher lung volumes (small airways close during exhalation → more trapped air → increased residual volume)

VO2 peak cross sectional and longitudinal studies

Letnes, Nes, and Wisloff 2023 compared cross-sectional and longitudinal studies of VO2 peak in adults

• found VO2 peak declines with age (men start at a higher VO2 peak than women)

• longitudinal data reveal greater rates of decline in VO2 peak compared with cross sectional studies

VO2 peak magnitude of decline

magnitude of decline in older ages is greater

15-20% decline / decade for women 70+ yrs of age

20-25% decline / decade for men 70+ yrs of age

aerobic capacity

relative aerobic capacity required for activities of daily living is different for younger adults vs older adults

• e.g. walking 7 km/hr is ~50% aerobic capacity for a 20 yr old while the same activity is ~90% aerobic capacity for a 70 yr old

muscle function

good muscle function is important for longevity (maintaining strength, mass, prevent disability, etc)

1. endocrine function

2. thermogenesis

3. systemic metabolism

4. storing amino acids

endocrine function

muscles release myokines, which influence other organs (e.g., liver, fat, brain)

• important for metabolic regulation and anti-inflammatory effects

thermogenesis

muscle generates heat during activity and shivering

• helps maintain body temperature, especially in older adults

systemic metabolism

muscle is a major site for glucose uptake → regulates blood sugar

• helps prevent insulin resistance and metabolic disorders

amino acid storage

muscle serves as a reservoir of amino acids

• important for repair, immune function, and protein synthesis during stress or illness

muscle mass and age

forearm cross-sectional area (muscle mass) decreases with age

Amara et al. 2003

muscle strength and age

grip strength (muscle strength) decreases with age

Amara et al. 2003

muscle mass and strength

does muscle mass fully account for changes in strength

• no because they do not decline with age at the same rate

• strength declines faster than mass

Amara et al. 2003

muscle strength decline rate

why does strength have a greater rate of decline than muscle mass with age

• other factors influence strength such as neuromuscular quality, fiber composition, and activation efficiency

force and age

force / cross sectional area decreases with age

• Amara et al. 2003

sarcopenia

progressive loss of muscle mass, strength, and/or physical performance associated with aging

• also, muscle mass ≥ 2 SD below the mean of young adults

dynapenia

loss of muscle strength and power that occurs with aging, not necessarily due to loss of muscle mass

Pollack et al 2015

investigated the relationship b/w age and physiological function in highly active older adults

• tried to identify a biological marker of aging

Pollack study rationale

many studies investigating physiological function have been confounded by other factors

• the study aimed to assess the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals, specifically cyclists aged 55–79 years

• minimized confounding factors

Pollack study findings

• VO2 max most closely associated with age but within the same age group, there was considerable variability in VO2 max levels despite homogeneity in PA levels among participants

• suggests other factors such as genetics or personal characteristics also play a role in the aging process

Pollack study connections

PA and prevention: research emphasizes the protective role of sustained PA in mitigating age-related declines in physiological functions

muscle and chronic disease

muscle has impacts on chronic diseases

1. obesity

2. type II diabetes

3. osteoporosis

obesity

muscle mass heightens energy expenditure

• ~10 kg difference in muscle mass can result in ~100 kcal/day difference in resting energy expenditure (Wolfe, 2006).

• more muscle → higher basal metabolism → easier weight management.

type II diabetes

muscle is the primary site for glucose uptakes

• maintaining healthy muscle mass and function improves glycemic control and reduces risk of diabetes progression

osteoporosis

muscle increases body mass

• body mass provides mechanical loading on bones → stimulates bone formation

• muscle contractions generate the largest voluntary forces on bones, crucial for maintaining bone strength.

phosphorylation capacity

refers to the mitochondria’s ability to make ATP from ADP + Pi during oxidative phosphorylation (maximal rate of ATP synthesis)

• significant reduction with age

Conley et al J Physiol 2000

mitochondrial content

how much mitochondria a cell has

• significant reduction in mitochondrial content with age

Conley et al J Physiol 2000

phosphorylation capacity per mitochondrial content

ATP-producing ability of each unit of mitochondria

• reduces with age

Conley et al J Physiol 2000

mitochondrial respiration

the process by which mitochondria use oxygen to make ATP from nutrients (mainly carbohydrates and fats)

• not much difference with age

Amara et al 2007

mitochondrial coupling

how tightly oxygen consumption is linked to ATP production

• how much oxygen it takes to produce ATP

• decreases with age

Amara et al 2007

free radicals

molecules such as damaged proteins or DNA that are eliminated by enzymes in the body

Free Radical Theory of Aging

free radicals build up in older adults

• can be toxic and impair synthesis, DNA

• can cause malfunction/become dysfunctional

muscle quantity vs muscle mass

Sarcopenia used to be thought of mainly as a loss of muscle mass.

• Now, evidence shows muscle quality (strength, power, endurance per unit of mass) declines even more.

• That’s why strength drops faster than mass with age (dynapenia)

mitochondria and sarcopenia

evidence for involvement of mitochondria in sarcopenia

• mitochondrial dysfunction = lower endurance, poorer recovery, weaker contractions → reduced muscle quality

reversible mitochondrial-related causes

not all mitochondrial-related causes are irreversible

• exercise training → boosts mitochondria biogenesis, improves coupling

Redman et al 2018

study that investigated the effects of long-term caloric restriction (CR) on metabolism and oxidative stress in healthy, non-obese humans

Redman study rationale

the study aimed to test two theories of aging

1. rate of living theory

2. oxidative damage theory

rate of living theory

proposes that organisms with higher metabolic rates age faster due to increased energy expenditure and associated damage

oxidative damage theory

suggests that aging results from cumulative damage caused by reactive oxygen species (ROS) produced during normal metabolic processes

Redman study key measures

The study employed several key measures to assess the effects of CR:

• Caloric Intake: Participants reduced their daily caloric intake by 25%.

• Body Weight: Average weight loss of approximately 8 kg over two years.

• Resting Energy Expenditure: Measured 24-hour and sleep energy expenditure to assess metabolic rate.

• Oxidative Stress: Measured urinary F2-isoprostane excretion as an index of oxidative damage.

• Hormonal Mediators: Assessed levels of hormones related to metabolism.

Redman study findings

study found that sustained CR in healthy, non-obese humans led to:

• Metabolic Slowing: Reduced energy expenditure beyond what could be accounted for by weight loss, indicating a slowing of metabolism.

• Reduced Oxidative Stress: Lower levels of oxidative damage, as evidenced by decreased urinary F2-isoprostane excretion

provide support for both the Rate of Living and Oxidative Damage theories of aging, suggesting that CR may slow metabolism and reduce oxidative damage, potentially influencing the aging process