Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians.

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.

Adiponectin levels and genotype: a potential regulator of life span in humans.

Although caloric restriction in numerous models extends life, longevity in humans is suggested to be limited by the increased prevalence of obesity. Adiponectin, a fat-derived peptide, has a protective role against age-related disease, and thus is an excellent candidate gene for longevity. We studied adiponectin levels in centenarians (n = 118), their offspring (n = 228), and unrelated participants <95 (n = 78). Adiponectin levels were significantly greater in participants older than 95 years (p =.01), an effect that was independent of sex and body mass index (BMI). Adiponectin levels in the offspring were higher (following adjustment for age, sex, and BMI) compared to controls (p =.02), suggesting that inherited factors play a role in determining adiponectin levels. Over-representation of two common variants in Adiponectin gene (ADIPOQ) in male long-lived individuals combined with their independent association with elevated plasma adiponectin levels (in men and women) suggests that their presence may promote increased life span through the regulation of adiponectin production and/or secretion.

Is there an association between acromegaly and thyroid carcinoma? A critical review of the literature.

Patients with acromegaly may have higher rates of cancer, possibly due to increased plasma levels of IGF-I, which is known to promote cellular growth. While simple and multinodular goiters are more common among acromegalics, reports of thyroid carcinoma are rare, and its true incidence is unclear. Here, we review the relevant literature in the context of a case of a patient with acromegaly with persistently elevated IGF-I levels who was subsequently diagnosed with thyroid carcinoma. The incidence and potential pathophysiologic mechanisms of benign and malignant thyroid disease in acromegaly are discussed. We conclude that in acromegalic patients with persistently elevated IGF-I levels, one should ensure careful monitoring of goiter and thyroid nodules, including fine-needle aspiration of nodules that are 1 cm or larger.