Aging across the body

p53 builds up when DNA is damaged. It holds the cell at a checkpoint while repair is tried, and it turns on apoptosis if the damage cannot be fixed.

• Correct: Stops the cell cycle and, if the damage cannot be fixed, triggers apoptosis:
• Copies the damaged DNA faster:
• Adds repeats to the ends of chromosomes:

Cardiac reserve is how much the heart can raise its output above rest. Training raises it; age and heart disease lower it.

• The blood stored in the veins:
• Correct: The gap between highest and resting cardiac output:
• The volume left in the ventricle after ejection:

Estrogen holds osteoclast activity down. When the ovaries stop making it, resorption outpaces formation and bone is lost faster.

• Correct: Estrogen, which restrains osteoclasts, falls:
• Calcitonin rises:
• Growth plates reopen:

At B the capacity curve sits between the two dashed lines. It still covers resting needs, so resting values are normal, but it no longer reaches the level a major stress demands. That shrinking gap is loss of reserve.

• Correct: Capacity still covers rest but not a major stress: Correct. Reserve, the gap between capacity and need, has closed for a major stress but not for rest.
• Capacity has already fallen below the level needed at rest: The curve at B is well above the resting line, which is why resting tests are normal.
• The resting need has risen with age while capacity held steady: The resting line is flat across all ages. What changes is capacity.
• Capacity is still the same as it was at point A: Capacity at B is about 55% of peak, compared with 100% at A.

DNA polymerase needs a primer and adds nucleotides to one end only. The gap left by the last primer at a chromosome tip cannot be filled, so a little of the end is lost each division. Telomerase could add repeats back, but most body cells make almost none.

• Reactive oxygen species cut off a fixed length at every division: Oxidative damage can speed telomere loss, but the loss at every division comes from the copying machinery itself.
• Telomerase removes repeats from the chromosome ends each time: Telomerase adds repeats; it lengthens telomeres.
• Apoptosis trims the chromosome ends before each division: Apoptosis kills the whole cell. It does not trim chromosome ends in a dividing cell.
• Correct: The polymerase cannot copy the chromosome's very end: Correct. This is the end-replication problem, uncorrected without telomerase.

Stopping division for good prevents a cell with damaged DNA from becoming cancerous. But senescent cells stay active, releasing cytokines and protein-digesting enzymes that inflame and damage their neighbors, and they accumulate with age.

• It speeds tissue repair but uses up the stem cells: Senescent cells do not divide, so they slow repair; they do not speed it.
• Correct: It blocks tumors but inflames nearby tissue: Correct. Tumor protection is the benefit; inflammatory secretions are the cost.
• It lengthens telomeres but raises the risk of cancer: Senescence does not lengthen telomeres; short telomeres are one of its triggers. It protects against cancer.
• It removes damaged cells by apoptosis but leaves gaps: That describes apoptosis, the other outcome of a checkpoint. A senescent cell stays alive.

A young, elastic aorta stretches as the ventricle ejects, blunting the systolic rise, and recoils in diastole, holding diastolic pressure up. A stiff aorta does neither, so systolic pressure rises and diastolic pressure stays level or falls.

• Correct: A stiff aorta no longer stretches and recoils with each beat: Correct. Lost elasticity widens the pulse pressure.
• The aging heart pumps a much larger stroke volume each beat: Stroke volume does not rise much with age. The pattern comes from the stiff arterial wall.
• Arterioles relax and widen with age: Relaxed arterioles would lower resistance and both pressures, not raise systolic alone.
• Blood becomes less viscous with age: Blood does not become thinner with age, and lower viscosity would lower pressure, not raise systolic.

Plasma creatinine depends on how much is made as well as how fast it is cleared. With little muscle she makes little creatinine, so even a reduced GFR keeps the level normal. eGFR corrects for age and sex and reveals the loss of nephrons.

• Her aging kidneys secrete creatinine faster than before: Creatinine is cleared mainly by filtration, and nothing speeds its secretion with age.
• Creatinine is no longer filtered by older glomeruli: Creatinine is filtered freely at any age; less of it is filtered only because GFR is lower.
• Correct: Less muscle makes less creatinine, masking a low GFR: Correct. Low production offsets low clearance, masking the fall in GFR.
• The eGFR formula ignores age and overestimates loss: eGFR includes age and sex, which is exactly why it is used to reveal the fall in GFR.

A new antigen needs naive T cells that happen to fit it. The thymus shrinks from puberty on and makes few new naive T cells, so the T cell pool fills with memory cells from past infections and fewer naive clones are available. B cell responses weaken too.

• Their memory cells from past infections have all died: Memory cells from past infections persist and come to dominate the T cell pool. The shortage is of naive cells.
• Correct: The shrunken thymus makes few new naive T cells: Correct. Fewer naive T cells means a narrower, weaker response to new antigens.
• Their antibodies no longer bind antigens well: Antibodies bind antigens normally; fewer and weaker new antibodies are made.
• Vaccines cannot reach the lymph nodes of older adults: Vaccines still reach the lymph nodes. The response there is what is weaker.

The lens stiffens in everyone with age, so near focus fails from the mid-40s. Dementia, anemia and incontinence all become more common with age but are diseases with causes to look for.

• Correct: Needing reading glasses: Correct. Presbyopia happens to everyone as the lens stiffens.
• Dementia with memory loss: Dementia becomes more common with age but is a disease; most older adults do not have it.
• Anemia on a routine blood count: Resting blood counts stay normal in healthy aging, so anemia has a cause to find.
• Urinary incontinence: Incontinence is common but not normal, and it often has a treatable cause.

Each system loses capacity through its own mechanism: fewer pacemaker cells and weaker sympathetic response in the heart, lost elastic recoil in the lungs, lost nephrons in the kidneys, net resorption in bone and a shrinking thymus in the immune system. Resting function is kept, but reserve falls everywhere.

• Maximum heart rate: down. The SA node loses pacemaker cells and responds less to sympathetic stimulation, so the highest rate falls by roughly 0.7 to 1 beat a year.
• Residual volume: up. Loss of lung elastic recoil lets small airways close earlier during expiration, trapping more air.
• Glomerular filtration rate: down. Nephrons are lost with age, reducing the total filtering surface.
• Bone mass: down. After about 30, osteoclasts resorb slightly more than osteoblasts rebuild in each remodeling cycle.
• Naive T cells in the blood: down. The thymus shrinks from puberty on and makes few new naive T cells.