I agree the observation by Hamilton defies the cumulative damage idea and the idea of a "switch" is more logical.
Furthermore looking from a broad view at Androgenetic Alopecia I believe that one component to it is "stress". Inflammation is often present that can even lead to fibrosis. Furthermore there are supporting studies for ROS, DNA damage and such that may have implications in Androgenetic Alopecia.
Since aging is a progressive decline to withstand stress and damage it is logical to assume that older (stem)cells would have more troubles coping with stress/damage than young ones.
Aubrey de Grey called hair loss a cell loss problem:
"Hair loss and grey hair are mostly a cell loss problem, and rejuvenating the epidermal stem cell population (as well as melanocytes specifically) is something a lot of people are making good progress on; check out the work of Elaine Fuchs and Fiona Watt and Colin Jahoda especially."
RepleniSens:
Every day, our cells are damaged by both tiny molecular-level insults and by obvious trauma. Some of these damaged cells are repaired, but others are either destroyed, or forced into a dysfunctional ‘senescent’ state where they can no longer divide, or commit ‘cellular suicide’ (apoptosis) for the greater good of the body. Some of the lost cells are replaced by the pools of specialized, tissue-specific stem cells, but the degenerative aging process makes these stem cell pools less effective at repair over time.
Check out Steve Horvath's paper:
DNA methylation age of human tissues and cell types
He found a set of 353 CpG sites, which he calls an "epigenetic clock", that correlate almost perfectly (correl = 0.96 in testing set) with age across many cell types. Some highlights:
- both embryonic stem cells and iPS cells have an "age" of about 0
- cells get "older" with each passage in culture
- genes around these CpG sites are enriched for cell death/survival, organismal/tissue development, and cancer
- rate of aging measured by the clock is highly heritable, but less so later in life (likely non-genetic effects in play)
- Aging is highly accelerated before adulthood; afterwards, it's approximately linear:
- DNAm age (clock age) is not related to mitotic age or cellular senescence
- DNAm age is accelerated in cancer cells
- He hypothesizes that DNAm aging is accelerated by an "epigenetic maintenance system" (EMS), which works to maintain epigenetic stability.
Predictions of this model:
- Cancer cells should show signs of accelerated aging, reflecting the protective actions of the EMS.
- Mitogens, genomic aberrations, and oncogenes, which trigger EMS, should accelerate DNAm aging.
- High age acceleration of cancer tissue should be associated with fewer somatic mutations given the
protective role of the EMS.
- Mutations in p53 should decrease age acceleration of cancer tissue, assuming p53 signaling helps trigger
the EMS.
He shows that all these predictions turn out to be true.
In
another paper, Horvat et al. also demonstrated that in the offspring of semi-supercentenarians, DNAm age is lower than expected based on actual age.
Anyway, I wonder if the mechanism of the A.G.A "switch" could also maybe involve some interaction between genetics and age-associated epigenetic changes such as these.