Shared phenotypes among segmental progeroid syndromes suggest underlying pathways of aging

Segmental progeroid syndromes are those whose phenotypes resemble accelerated aging. Here we analyze those phenotypes and hypothesize that short telomeres produce the same group of symptoms in a variety of otherwise unrelated progeroid syndromes. Specific findings are the following: (a) short telorneres in some progeroid syndromes cause an alopecia/osteoporosis/ fingernail-atrophy group of symptoms; (b) fingernail atrophy in progeroid syndromes resembles the natural slowing of nail growth that occurs in normal aging and nail growth velocity, and may be a inarker of replicative aging in keratinocyte stern cells; (c) alopecia and reduced hair diameter parallel the nail results; (d) osteoporosis in Dyskeratosis Congenita resembles age-related osteoporosis, but the same is not true of other progerias; and (e) bray hair is associated with short telorneres, but may also involve reactive oxygen species. On the basis of these results, we make several predictions and discuss how the segmental quality of progeroid syndromes may provide insight into normative aging.