How Research on Human Progeroid and Antigeroid Syndromes Can Contribute to the Longevity Dividend Initiative

Abstract

Although translational applications derived from research on basic mechanisms of aging are likely to enhance health spans and life spans for most of us (the longevity dividend), there will remain subsets of individuals with special vulnerabilities. Medical genetics is a discipline that describes such "private" patterns of aging and can reveal underlying mechanisms, many of which support genomic instability as a major mechanism of aging. We review examples of three classes of informative disorders: "segmental progeroid syndromes" (those that appear to accelerate multiple features of aging), "unimodal progeroid syndromes" (those that impact on a single disorder of aging), and "unimodal antigeroid syndromes," variants that provide enhanced protection against specific disorders of aging; we urge our colleagues to expand our meager research efforts on the latter, including ancillary somatic cell genetic approaches.

Figure 1.

Examples of progeroid patients and selected causal genes for segmental progeroid syndromes. (A) A 35-yr-old Italian Caucasian male, registry #ROMA1010, with a homozygous WRN mutation, c.867_874delAGAAAATC (p.Glu290fs) (Friedrich et al. 2010). He had a characteristic ankle ulcer (with bandage). (B) A 23-yr-old African–American Caucasian female, registry #ATLAN1010 with a heterozygous LMNA mutation, c.398G>T (p.Arg133Leu) (Chen et al. 2003). Atrophic skin of hands is shown. (C) Examples of major causal genes of segmental progeroid syndromes associated with DNA damage repair and response. Mutated loci so far identified among cases of atypical Werner syndrome (WS) within the International Registry of WS are underlined.