Physiology of Senescence Flashcards
What is the difference between primary and secondary aging?
Primary aging is related to intrinsic changes that occur with age unrelated to disease and environmental influences.
Secondary aging is related to changes caused by the interaction of primary aging with environmental influences or disease processes
Why is aging inescapable?
Mutation accumulation: Any mutations that result in a post-reproductive reduction in fitness will not be removed by natural selection if they benefit youth selective fitness.
Antagonistic pleiotropy: A gene that exerts a small pre-reproductive benefit and a large post-reproductive cost will still be selected for. P53 activating mutations (Anti-tumour, decreased lifespan)
What is antagonistic pleiotropy?
A gene that exerts a small pre-reproductive benefit and a large post-reproductive cost will still be selected for. P53 activating mutations (Anti-tumour, decreased lifespan)
What are the theories for primary aging?
2 theories:
Programmed theories: Neuroendocrine (Biological clock and endocrine control), Immune (Immune system is pacemaker of aging), Finite cell division (cells stop dividing due to hayflick limit after a finite number of divisions)
Wear and Tear theories:
Free radicals, DNA damage, aggregation of proteins that isn’t cleared, recycling failure (old/dysfunctional proteins are not cleared)
How does oxidative stress cause aging?
They cause damage to sugars (glycation), mitochondria, and DNA
What mechanisms of aging are caused by inadequate repair?
DNA damage due to deficient repair mechanisms (Telomere shortening)
Protein turnover (Ubiquitin and autophagy)
Membranes (Lipid peroxidation)
Cell number homeostasis problems (Cell removal increases due to apoptosis and necrosis but division is limited by telomeres and the Hayflick limit)
What induces senescence in cells?
Telomere dysfunction
Chromatin perturbation
DNA damage
Strong mitogenic signals
These factors induce senesence phenotypes such as:
Growth arrest
Functional changes
Resistance to apoptosis
Why is cellular senescence used to understand ageing?
Accumulation of senescent cells predicts lifespan (across various tissues, multiple mouse strains, both ad libitum fed and caloric restriction, gammaH2AX:PCNA
What changes in the physiology of the human body with age?
Brain weight
Basal metabolism
Kidney filtration rate
Maximal breathing capacity
What happens to body composition with aging?
Drop in lean body mass (muscular and skeletal mass)
Drop in total body water
Increase in adipose tissue
What happens to cells with aging?
Increased DNA damage and decreased DNA repair capacity
Decreased oxidative capacity
Accelerated cell senescence
Increased fibrosis, lipofuscin accumulation (oxidised protein/lipid lysosymes)
What is sarcopaenia?
During the late 30s muscle mass starts to drop at a rate of 1 - 2% mass/year.
Myofiber size and number both decrease (mostly type 2 fibers)
Number of motor units also decreases with aging
Can be caused by myogenic or neurogenic mechanisms (Inactivity leads to less type 2 fiber use. MN loss leads to atrophy.
How can sarcopaenia be prevented?
Strength training increases myofiber size and muscle mass
What happens in bones with aging?
Bone remodelling starts to favour osteoclast activity in middle age. Resorption starts to be quicker than formation of bone leading to progressive mass loss
Menopause accelerates loss (loss of oestrogen protective effects)
What happens to joints with aging?
Joint flexibility decreases
Articular cartilage thins
Less tensile stiffness
Fatigue resistance decreases
Strength decreases
Loss of elasticity, tendency towards osteoarthritis
What happens to the central nervous systems with aging?
CNS atrophy (0.1% per year from 20 to 60 years of age and 0.5% after 70)
Aggregates accumulate
Decreased neurotransmission
Cell death is seen most in the cortex and hippocampus leading to bigger ventricles.
What happens to the peripheral nervous system with aging?
Reduced regenerative response (decreased number of schwann cells and increased macrophage response)
Demyelination/axonal atrophy/electropphysiology –> Slowed conduction
Damped signal transduction
Decreased beta-adrenergic and muscarinic responsiveness
Decreased response to beta-blockers
What happens to sensory functions with aging?
They all deteriorate. (touch, vibration, spatial distinction, proprioception, vestibular function, hearing, vision, central processing (difficulty distinguishing spoken words from background noise)
What happens to motor function with aging?
Decreased reaction time including decreased simple responses and complex responses.
Slowing of central processing also due to muscle strength decrease
What happens to cognitive functions with learning?
Intelligence, memory and learning decline with advancing age
Certain types of memory deteriorate not all. Other types of memory are not lost.
What happens to cardiovascular function with aging?
Vascular: Decreased arterial compliance and distensibility (higher systolic BP)
Increased cardiac afterload
Decreased ejection fraction and diastolic relaxation
Decreased intrinsic and max HR
Atrioventricular conduction time increases
Blunted baroreflex leading to postural hypotension.
What happens to pulmonary function with age?
Decreased respiratory muscle strength and endurance (Atrophy of type 2a myofibers)
Lung volumes drop gradually
Decreased lung elasticity (Collagen and elastin degenerate, small airways collapse, impaired ventilation increased V/Q mismatch decreased resting PaO2)
What happens to exercise capacity with aging?
Max O2 uptake declines
Muscle mass decreases
CV/pulm function drop leading to the other problems.
Decreased response to physical conditioning but skeletal muscle and CV system remain responsive to exercise in centenarians.
What happens to kidney and urinary function with age?
Decreased renal mass
Decreased tubular mass
Loss of bladder capacity, void rate, and there is an increase in residual volume after urination.
Changes in Na+ load
RBF and GFR both fall with age as well.
