Aging FN-4520

Life Expectancy

Average number of years for a population of individuals (usually expressed from birth)

Reasons life expectancy is different for different ages, genders and ethic backgrounds

-Diet
-Genetics
-Environmental factors
-Healthcare availability

Why life expectancy is lower in third world countries

-Birth trauma
-Healthcare accessibility
-Decreased resources
-Finances

Reasons we've lost 3 years off our lives in the past 2 years

-Covid affecting the elderly
-Decrease exercise and socialization with lockdown
-Long covid effects
-Epidemiology focused studies

Generational Cohorts

People who are likely to experience common environmental conditions or events

Generation Cohorts and their years

Baby Boomers - 1946-1964
Generation X - 1965-1979
Millennials - 1980's-1994
Generation Z - 1995-2012

Gender differences in life expectancy

-Women outlive men by 4-10 years on average
-Gap increased between 1920-1970
-Leveled off at 1970's with smoking publicly declared bad
-Men usually have riskier jobs, less likely to seek healthcare

Genetic theories: Why women live longer

Two copies of X chromosome provides protection for women.

Hormonal theory: Why women live longer

-Estrogen: protective effect on coronary artery disease
-Increase HDL, decrease LDL, acts as antioxidant
-Promotes faster immune response, resistant to cancers
-Can promote auto-immunity (Lupus, MS)

-Testosterone: decrease HDL, increase LDL
-Decrease immune function
-REgulates gene expression for immune cell production

Social explanations: Why women live longer

-Males tend to be in more dangerous/stressful work environments
-Males display more risk or harmful behaviour
-Men less likely to access health care

Irony of the Gender Gap

Women outlive men, but also tend to live with more non-fatal and chronic conditions
-May compromise quality of life
-May result in more frequent health care access

Reasons for changes in population pyramids

-Decrease in child mortality
-Control of infection diseases
-Decreased premature adult death
-Enhanced living conditions and advances in medical care

Socioeconomic influences on aging

-Lower life expectancy for black people
-Underdeveloped countries: high birth rates, poor social security, malnutrition, disease, economic hardship, political conflict, poor health care
-Economics, marital status, education

Aging definition

A process or group of processes that occurs in living organisms that with the passage of time lead to the loss of adaptability, functional impairment, and eventual death

Primary Aging

Universal changes within a species that are expected to occur across time, not related to disease
must be deleterious, progressive, intrinsic, universal

Secondary Aging

Clinical symptoms that includes the effects of environment and disease
Results from preventable/modifiable behaviours:
sedentary lifestyle, smoking/drinking/drugs, poor diet, disease, stress

Chronological vs biological age

-Chronological: Age based on the duration of time you have lived
-Biological: "Functional" age in comparison to the average abilities of different chronological ages
-NOT independent of each other, highly interactive

Biomarkers (criteria)

-Must predict aging rate to a reasonable degree
-Must be more sensitive to aging that chronological age
-Must be something that can be tested repeatedly without harm
-Must be a process that works in humans and lab animals

"Quantification of biological aging in young adults" article

-1000 young adults, measured 18 biomarkers that reflect function of organs and DNA characteristics
-Used a formula to "predict" biological age
-Found different biomarkers are more predictive of age
-Chronological and biological age should be similar, but there are outliers
-Wearables can be low-cost and practical way to measure biological age

Senescence (process)

The condition of process of deterioration with age

Senescence (state)

Loss of fidelity, state of disfunction, loss of reserve capacity, loss of adaptability

DNA

Found in nucleus, contains our genetic code which consists of countless pairs of bases (A,G,T,C)

Gene

Cluster of DNA that acts as instructions for transcription into RNA, which can be coded into proteins. 99% of the genetic code is identical between humans

Chromosome

Group of genes (23 pairs), DNA is wound tightly around histones to maintain shape, coil of DNA around histone is a nucleosome

How genetics influence aging

-Gene expression
-DNA sequence
-Telomere length

How we can influence our genetics

-Diet and exercise: changes in genes related to antioxidant activity, mitochondrial health, DNA maintenance and repair, histone modification
-Nutrigenomics

Single nucleotide polymorphisms (SNP)

-Mutation of a single base pair
-Can potentially change gene product
-Some are harmless, some derail gene function
-Can change or stop protein synthesis, or cause uncontrolled replication (cancer)

Genetic contribution to aging - inheritance

Not a strong correlation between parent's lifespan and offspring lifespan

Genetic contribution to aging - Twin studies

40% of similarities in lifespan explained by shared genetics between identical twins

Progeria

-"prematurely old"
-most severe aging disease
-extremely rare (1/8 million)
-live to mid teens-early 20s
-alopecia and skin conditions/abnormalities
-severely stunted growth
-loss of muscle and fat
-caused by Latin A gene mutation in one parent (integral protein of nuclear membrane)

Werner Syndrome

-Rare (1 in 200,000)
-Live to late 40s
-develop normally until puberty
-no "growth spurt" associated with puberty
-symptoms of premature aging
-caused by WRN gene mutation (autosomal recessive)
-affects DNA repair and replication

Evolutionary theories of aging

-Change in heritable characteristics of biological populations over successive generations
-Natural selection
-aged individuals weaken species
-Programmed theory: people are programmed to die
-once people have reproduced, they are a waste of space

Counterargument to evolutionary theories of aging

-Genes don't "know" elderly become a burden to species survival
-only reproducing individuals affect species evolution
-Grandmother hypothesis: have older people around allows younger families to have more children give some help can be provided (multigenerational families)

Damage theory of aging

-Aging is the result of accumulation of tissue/cellular damage throughout life
-Dysfunction->senescence->death
-Lack of repair capacity, can't keep up with cell maintenance demands

Waste accumulation theory

-Aging results In accumulation of cellular debris, impairs cell function
-Lysosomes remove waste, but lysosome dysfunction leads to aging

DNA damage causes

-Mutations/deletions/structural instability
-Environmental toxins
-UV rays from sunlight
-Poisons from food
-Metabolic by-products
-Apoptosis
-Cancer
-Senescense
-Impaired DNA repair (SMOKER STUDY, highly protective genes enhance repair capacity)

Free Radicals

-Atom that has lost an electron during oxidation
-Unstable atom that will try to take electrons from other atoms
-Oxygen as a free radical: reactive oxygen species (ROS)
-antioxidants donate electrons to stabilize

Free radical causes

-Environmental factors (pollution, UV rays, toxic substances, radiation, tobacco smoke, asbestos)
-metabolic processes (energy metabolism, immune system response, exercise)

Parts of cells that free radicals damage

-Proteins
-Phospholipid bilayer
-LDLs
-DNA

Diseases linked to free radical accumulation

-Heart diseases
-Cancers
-Diabetes
-Cataracts
-Alzheimers
-Parkinsons

Mitochondrial theory of aging

-Free radicals are produced in close proximity to mitochondria
-can induce vicious cycle of ROS damage
-ETC mistakes result in more superoxide ions
-Maternally inherited mitochondrial DNA, mDNA damage leads to mitochondrial heteroplasmy (affects mitochondrial replicaition)

How we protect ourselves from free radicals

-Endogenous antioxidant enzymes (superoxide dismutase, catalase)
-Dietary antioxidants (Vitamin E, C)
-Endurance exercise increases long term antioxidant defences

Rate of living theory

-Faster metabolic rate = lower life span
-Calorie restriction been shown to increase lifespan by 50% in some lab animals
-Human studies: did not restrict far enough, increased thymus and T cell count
-Rodents: increased lifespan, but reduced growth, reproductive viability and immune defence

Gradual imbalance theory of aging

-Immune and neuro-endocrine system decline
-increased susceptibility to disease/infection
-decreased autoimmunity

Immune imbalance

-T cell function declines with age
-Killer Tcells fight foreign bodes, helper cells produce antibodies
-Tcell maturity in thymus (shrinks as we age, reduced to 10% by age 50)

Neuro-endocrine imbalance

-Leads to hormonal change, nervous system dysfunction, tissue pathology, movement disorders, accelerated aging
-Proper communication between systems is essential for feedback loops, homeostasis, metabolism, cell repair/maintenance
-Aging is result of de-sensitization of tissues to hormones, overproduction or hormones, decreased secretion

Hypothalamus-pituitary axis (HPA axis)

Regulates nervous system function, behaviours, sleep/wake cycle, endocrine, metabolism, stress response

Growth hormone pathways

Ghrelin (stomach) and GHRH (hypothalamus) drive pituitary to release GH to liver, drives release of IGF-1 to bone, muscle, adipose tissue. Somatostatin inhibits GH release

hormone replacement therapy (HRT)

-Supplementing declining hormone levels (E/T) with synthetic or exogenous hormone to restore early adulthood levels
-Cognitive and muscular and skeletal benefits, long term effects unknown

Quality of life factors

-Health and fitness
-Cognitive and emotional
-Social and recreational
-Economic status

Morbidity + causes

"Condition of being diseases" -> physical/mental disability by chronic disease results in lack of independence
-Causes: musculoskeletal diseases, atherosclerosis, cancer, diabetes, emphysema, liver cirrhosis

Health-adjusted life expectancy (HALE)

Average # of years that a person can expect to live in "full health" by taking into account years lived in less than full health due to disease/injury

Lifestyle role in morbidity compression

Person with lower health risks will have disability later in life, less disability at any age, less cumulative disability
-NEJM study: assess smoking, BMI, PA -> ~7 less yearsoof morbidity

Dallas Fitness Study

-30,000 people, Vo2max assessment over 8-20 years
-Death rate was higher for least fit people
-Higher death risk for low fitness than SBP>140mmhg, BMI, CHOL, smoking

Harvard Alumni Health Study

-N=17,000
-Volume effect: greatest benefit at 2000-3500kcal/week activity, 25-30% decrease in morality rate
-Age effect
-intensity matters: people who burned 50% of cals with virgorous training (MET>6) showed benefit regardless of TEE

MET

1 kcal/kg/hour, equal to energy cost of sitting quietly (3.5ml/kg/min)

MET/h

Less active and more sedentary older adults

-10hr/day sedentary time
-15 MPA, 2 min VPA
-Only 11% older adults meet PA guidelines

Mechanisms of exercise on aging

-Delays, prevents, reverses chronic age
-Improve antioxidant systems
-Longer telomeres

4 general training principles

-Individualization
-Specificity
-Reversibilty
-Progressive overload

Principle of Individualization

Prescribing exercise with the purpose of meeting one's personally important needs and goals

Principle of Specificity

-Exercise adaptations are specific to mode and intensity of training
-Seniors: prioritize ADLs to focus on independent in self-care and hygiene
-Consistentcy ADLs results in training effect
-Incorporate PA throughout the day rather than relying on intentional exercise
-Barthel Index of ADLs

Principle of Reveresibility

"Use it or lose it"
-detraining: gradually reverse all gains, or accelerate age-related function changes
-brief inactivity periods more severe for seniors

Principle of Progressive Overload

-Increase demands on the body to create further adaptation
-Must be applied more gradually for seniors (higher injury risk, slower adaptation)

Key components in PA programming

-Client centered
-Goal driven
-Include measurable outcomes, functional activities, screening, safety focus

Canada PA guidelines, adults vs older adults

-150min moderate-vigorous aerobic PA, in bouts of 10+mins
-Strength training 2+ days a week
-Seniors with poor mobility should enhance balance and prevent falls

Aerobic exercise intensity

-For healthy people: a brisk walk intensity
-RPE: 4-6 out of 10

Resistance training guidelines

-Beginner: 1 set 10-15 reps, of 8-10 exercises, 2 days/week
-Start with minimal resistance, progress to 50-8-% 1RM
-2-3 min rest period between exercises

Exercise selection criteria

-Preference
-Equipment accessibility
-Experience
-Safety
-Convenience

Flexibility training

-Evidence is conflicting on usefulness
-Recommendation: slow, static stretch to tension, hold 10-30 sec, 60sec if possible
-Should not be done until 2-3 months post fracture

Special safety considerations for seniors

-Dehydration
-Blisters/foot ulcers
-Surface area/friction
-Awareness of signs/symptoms of health problems
-avoid Valsalva maneuver

Seniors Fitness Test: Assessment and Exercises

-Assessment of: strength, balance, endurance, flexibility, mobility
-Includes 30sec sit-to-stand, arm curl, 6min walk, chair sit-and-reach, back scratch, 8-foot Up and Go

30sec sit-to-stand

-Sit up and down AMRAP for 30sec
-No arms used
-Healthy seniors should be able to do at least 14 reps

Arm curl

-5lb for female, 8lb for male
-AMRAP 30sec
-Healthy females, 12 reps
-Healthy males, 15 reps

6min walk test

-Walking 6min as fast as participant is able to
-Healthy males 65years: 690m
-Healthy females 65: 631m

Chair sit-and-reach

-17-inch chair (normal chair)
-Bend one leg, straighten other, reach for toes
-Healthy seniors: reach within 3inch from their toes

Back stratch

One hand over shoulder, one behind back, measure distance between fingers, repeat both sides
-Healthy seniors should be between 1.0-7.5 inches apart

8-foot Up and Go

-Start in chair, walk around cone 8ft away, back to chair, as fast as comfortable without running
-Healthy males: 5.7sec
-Healthy females: 6.4sec

Body composition changes across the lifespan

-Decrease in height (change in posture and spine structure)
-change in hair and skin pigmentation
-decrease in lean body mass (change in body comp)

Anthropometric weight changes

-Males lose ~40s, slow decline
-Females continue to gain weight
-Could be affected by selective survival, cohort effects, actual/sudden weight loss

Fat mass vs fat free mass

-Fat: essential (cell membranes) and storage (visceral, subcutaneous)
-Fat free: water, proteins, bone minerals

Sedentary - Effect on body mass

Decrease caloric expenditure, leads to weight gain, increased fat mass and decreased muscle mass

Nutritional risks with aging

-Caloric intake > expenditure (half of cals from processed foods)
-Risk of malnutrition
-Cachexia (massive body tissue lost)

Mechanisms underlying changes in body mass/composition

-Fat mass > fat-free Macs leads to decreased BMR
-Decreased skeletal muscle and liver mass
-Metabolic changes -> decreased # mitochondria, increased heterplasmy, decreased beta-oxidation

The Obesity Paradox

Obesity becomes less of a risk factor for all-cause mortality as we age

Functions of the skeleton

-Mechanical support
-Reservoir (minerals, systemic regulatory hormones, bone marrow, blood/immune cell production, calcium)
-Protection

Bone composition

-Living tissue; cells are embedded in mineralized matrix (contains hydroxyapatite, made from calcium and phosphate)
-Matrix consists of dense proteins as scaffold (Type 1 collagen)
-Compact (cortical) and cancellous (trabecular) bone

Compact (cortical) bone

-75% of total skeletal mass, 33% total bone surface area
-Found in long bone shaft, surface of flat bone
-Very dense and strong
-Matrix comprised of lamellae rings (osteon)

Cancellous (trabecular/spongy) bone

-Found in spine, pelvis, ends of long bone
-67% of volume, 25-30% of bone mass
-Light, flexible and strong

Bone as a dynamic tissue

-Constant remodelling
-Osteoblasts (formation)
-Osteoclasts (resorption)
-Osteocytes (maintenance)

Bone metabolism as we age

Youth: formation>resorption
Young adult (30): formation = resorption
Past age 30: resorption > formation
Past age 50: RESORPTION > formation

Measurement of bone

DEXA: bone mass, bone mineral density
NMR: bone mineral content

Osteopenia vs osteoporosis

Osteopenia: decreased bone mass with age: BMD 1-2.5 SD below mean
Osteoporosis: decrease bone mineral density resulting in high risk of fragility fracture: BMD >2.5 SD below mean

Two main types of osteoporosis

Primary: age-related loss of BMD
Secondary: loss of BMD due to other factors (disease, medication, etc)

Osteoporosis prevalence in Canada

1 in 4 women, 1 in 8 men over the age of 50

Risk factors associated with osteoporosis

-Females (less calcium consumption, less peak bone mass, estrogen reliance for bone metabolism)
-Physique (lower BW, leaner, lower muscle mass, lower BMI)
-Lifestyle (sedentary, low/no impact activity, smoking, alcohol)
-Diet (Low calcium, magnesium, vit D, lactose intolerance)
-Profile (Caucasian or Asian, family hx)

Hip fractures and osteoporosis

-Hip fracture risk DOUBLES with every 10% BMD decrease
-Hip, spine, wrist are common fracture sites
-Occurs twice as often in females
-Low BMI women have twice the risk compared to high BMI women

Vertebral fracture

One or multiple "crush" fractures can result in a Dowager's hump

Factors that regulate bone changes with age

-Hormonal changes
-Diet
-Exercise

Hormonal changes - Bone changes

-Estrogen: loss post-menopause accelerates bone loss
-increased uncoupling between resorption and formation
-decreased calcium absorption from intestine (secondary osteoporosis?)
-Supplements not very effective

Diet - Bone changes

-Calcium, vit D deficiencies are common
-Calcium, Vit D, Magnesium needed for bone metabolism
-Can supplement calcium, commonly with Vit D, for optimal bioavailability