General ageing and functional decline Flashcards
functional decline
a reduction in ability to perform self-care activities of daily living (ADL) because of a decrement in physical or cognitive functioning
sarcopenia (definition)
Sarcopenia is a type of muscle loss (muscle atrophy) that occurs with aging (primary) and/or immobility/disease (secondary). It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength
sarcopenia (mechanism)
- loss of MHC2A and x molecules –> degeneration of type 2 fibers, they shrink (fast twitch)
- grouping of type 1 and 2 fibers
- co-expression of MHC1 and 2 on the same fiber
- satellite cell population of type 2 fibers decreases
- anabolic resistance (type 2 fibers and their satellite cells)
- loss of innervation (smaller axons and loss of motor end plates, and possible loss of whole motor neurons)
- endocrine dysfunction (less GH, IGF, sex hormones, thyroid hormones, etc.)
- mitochondrial dysfunction –> ROS –> inflammation/inflammageing
sarcopenia treatment and prevention
- Exercise and adequate protein diet is the main form of prevention
- Treatment: resistance training, leucine supplementation
• Future treatments include testosterone and anabolic steroids, ghrelin agonist and myostatin antibodies
• Myostatin, a member of the transforming growth factor-β superfamily, is a negative regulator of muscle growth and strength so creating antibodies against it might increase muscle growth
• Ghrelin agonists like anamorelin cause greater food intake and GH release causing increased muscle growth (not yet proven that it I accompanied by increased strength)
osteoarthritis - definition
- Mechanical wear of joints, an active disease process in the articular cartilage that ultimately affects the entire joint
• Most common in knee
• Leads to pain and disability
osteoarthritis structural changes
- holes in the articulate cartilage (bone exposure)
- damage to ligaments
- osteophytes (bone outgrowth, repair mechanism attempts to repair cartilage loss but results in bony outgrowths)
- subchondral microdamage
- during later stages there is bone tissue where there should be cartilage
osteoarthritis mechanism
- Cartilage cells become activated and start to:
secrete matrix-degrading enzymes
release inflammatory cytokines
release collagen type x –> increased mineralisation
osteoporosis - definition and effects
- Systemic skeletal disease characterised by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility
• Loss of collagen type 1, osteocalcin, Hydroxy apatite and Alkaline phosphatase - Leads to acute and chronic pain, kyphosis (round back), loss of height, loss of mobility, bulging abdomen (GI problems), breathing difficulties, depression and loss of independence
- The main acute issue if the increased risk for fractures
primary osteoporosis
- gonadal deficiency: age associated drop in sex hormones results in a disbalnce between obsteoblasts and clasts in favour of clasts
- Oestrogen withdrawal (menopause) will lead to osteoclastogenesis via RANK signalling –> increased bone matrix reabsorption
- Oestrogen withdrawal also leads to increased cytokine production that leads to bone reabsorption (IL1, IL11 and TNF-alfa and IL-6)
- Androgen receptors are present on osteoblasts, testosterone and dihydroxytestosterone both stimulate osteoblast differentiation. Testosterone may also increase skeletal and circulating IGF1 (needed for muscle mass and bone mass)
• Since testosterone drops 1% a year after 30 bone mass will eventually follow this curve
• Osteoblasts will not differentiate properly
secondary osteoporosis
any other condition that influences bone matrix:
- diabetes
- arthritis
- cancer
- inflammation (due to age): over active osteoclasts due to RANK signaling via inflammatory cytokines
vitamin D
- Vitamin D deficiency causes soft bones in children (rickets disease)
- Vitamin D is required from taking up calcium from food, so collagen is produced but not mineralised in bones leading to bending bones
- together with calcium supplementation main prevention against osteoporosis
osteoporosis treatment
- Bisphosphonates: bind with high affinity to the mineral matrix of the bone and inhibit osteoclast resorption of the bone, leading to a decrease in bone turnover and a net gain in bone mass
- RANKL inhibitors: IgGs that neutralise RANKL so there is no binding to RANK receptors in osteoclasts and thus less differentiation and bone reabsorption
menopause
Menopause is the sharp decrease of oestradiol and progesterone production by the ovaries (cells of the follicles) due to the depletion of the finite amount of oocytes
• After menopause, oestrogen continues to be produced mostly by aromatase in fat tissues
–> results in high FSH and LH (not used by ovaries) in blood but low eostrogen
andropause
- Late-onset hypogonadism is an endocrine condition as a result of aging: steady slow decline in testosterone levels in males
- It is caused by primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary failure)
• Primary hypogonadism: less Leydig cells in older men and less responsive LH receptors in older men
• Secondary hypogonadism: decreased GnRH production in older men and thus less LH and FSH so less testosterone production
somatopause
The progressive decline in the levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) - the hormones of the hypothalamic–pituitary–somatotropic axis (HPS axis)
- leads to decreased lean body mass (less bone and muscle more fat)
