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Thomas T Perls

Publications and source records attributed to Thomas T Perls.

At least 19 recordsLinked to original sources
PubMed2024

Cross-platform proteomics signatures of extreme old age.

In previous work, we used a SomaLogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood generated in an independent set. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals. The comparison with blood transcriptomics also highlights a possible role for neutrophil degranulation in aging.

Humans↗
PubMed2006

The different paths to 100.

Many people believe that the older a person gets, the sicker he or she becomes. The result can be quite a pessimistic view of very old age. If this were true, most if not all centenarians would have significant disability. However, approximately 90% of centenarians in a population-based study were functionally independent at the average age of 92 y. Thus, to achieve extreme old age, a much more enabling point of view emerges: the older an individual gets, the healthier he or she has been. Centenarians thus have the potential to represent a model of relative resistance to age-related diseases and slower aging. Currently, 1 in every 10 000 persons in the United States is 100 y of age or older. This prevalence is quickly changing, however, and it is likely that most industrialized nations will soon experience twice that prevalence, or one centenarian per 5000 persons. The ability to survive to extreme old age appears to be the result of a complex combination of genetics, environment, lifestyle, and luck. Understanding the genetics of the very old, and identifying the molecular drivers of longevity (or of mortality), is a potentially powerful approach to discovering and targeting the pathways mediating aging and disease susceptibility and developing preventive and therapeutic agents that will allow more of the population to age in good health.

Aged↗
PubMed2006

Characteristics of 32 supercentenarians.

OBJECTIVES: To report phenotypic characteristics of 32 age-validated supercentenarians. DESIGN: Case series. SETTING: U.S.-based recruitment effort. PARTICIPANTS: Thirty-two supercentenarians. MEASUREMENTS: Multiple forms of proof were used to validate age claims. Sociodemographic, activities of daily living, and medical history data were collected. RESULTS: Age range was 110 to 119. Fifty-nine percent had Barthel Index scores in the partially to totally dependent range, whereas 41% required minimal assistance or were independent. Few subjects had a history of clinically evident vascular-related diseases, including myocardial infarction (n=2, 6%) and stroke (n=4, 13%). Twenty-two percent (n=7) were taking medications for hypertension. Twenty-five percent (n=8) had a history of cancer (all cured). Diabetes mellitus (n=1, 3%) and Parkinson's disease (n=1, 3%) were rare. Osteoporosis (n=14, 44%) and cataract history (n=28, 88%) were common. CONCLUSION: Data collected thus far suggest that supercentenarians markedly delay and even escape clinical expression of vascular disease toward the end of their exceptionally long lives. A surprisingly substantial proportion of these individuals were still functionally independent or required minimal assistance.

Activities of Daily Living↗
PubMed2005

Cancer in the oldest old.

Our previous work revealed that 88% of centenarians delay or escape the age-related lethal diseases cardiac disease, stroke and diabetes. In the cases of those having a history of cancer we have observed anecdotes of centenarians presenting with large primary tumors that would have otherwise been expected to have metastasized and to have been lethal. However, these tumors were removed without consequence. To better understand the relationship between cancer and exceptional longevity, we quantified age of cancer diagnoses, life-time clinically evident cancer prevalence, tobacco use and family histories through medical record review and interviews. One thousand one hundred and forty-three subjects were studied revealing 20% (N=152) of female and 22% (N=80) of male centenarians with a history of non-skin cancer. The most common cancers were prostate (11.7% of males), breast (8.2% of females), and colon (5.7%). The average age of diagnosis was 80.5 years compared to 63.2 years in the general population according to National Cancer Institute SEER data. Similar delays were noted when age of onset was examined according to specific type of cancer. In conclusion, the age of diagnosis of cancer is relatively delayed in those who live to 100 years. Some cancers are very rare among these individuals suggesting that there are certain cancers that may be incompatible with survival to extreme old age.

Age Factors↗
PubMed2004

First autopsy study of an Okinawan centenarian: absence of many age-related diseases.

Consistent with the compression-of-morbidity hypothesis, several studies have reported that a significant proportion of centenarians delay or escape age-related diseases. Of those who live with such diseases for a long time, many appear to do so with better functional status than do younger persons who do not achieve extreme old age. The authors describe the first autopsy in an Okinawan-Japanese centenarian who escaped many age-related illnesses and delayed frailty toward the end of her very long life. Her late-life morbidity pattern is contrasted with that of white centenarians.

Aged↗
PubMed2004

Cardiovascular disease delay in centenarian offspring.

BACKGROUND: Previously, the authors have shown that an important component of the ability to survive to exceptionally old age is family health history. This study assessed the age at onset of age-related diseases in centenarian offspring. METHODS: The health histories of 177 offspring of centenarians enrolled in the nationwide New England Centenarian Study, and 166 controls were assessed from 1997 to 2000. Controls were the offspring of parents born in the same years as the centenarians but at least one of whom died at average life expectancy. Ages at onset of heart disease, hypertension, diabetes, cancer, osteoporosis, cataracts, glaucoma, macular degeneration, depression, thyroid disease, and stroke were compared in the two groups. RESULTS: The median ages of onset for coronary heart disease (p <.001), hypertension (p <.001), diabetes (p =.002), and stroke (p =.017) were significantly delayed in the centenarian offspring by 5.0, 2.0, 8.5, and 8.5 years, respectively, compared with the age-matched controls. Adjusted hazard ratios were 0.388 (p =.0004), 0.39 (p <.0001), 0.302 (p =.008), and 0.328 (p =.06). No differences were found in the ages of onset for the other diseases investigated. CONCLUSIONS: The offspring of centenarians show a marked delay in the age of onset for cardiovascular disease, diabetes, hypertension, and stroke but not for other age-related diseases such as cancer, osteoporosis, and thyroid disease. These results suggest that the children of centenarians may be following in their parents' footsteps, markedly delaying the onset of lethal diseases that commonly affect older persons.

Aged↗
PubMed2004

Anti-aging quackery: human growth hormone and tricks of the trade--more dangerous than ever.

To assess the presence of quackery in the anti-aging industry, the Internet was surveyed for web sites marketing anti-aging products as well as those providing consumer advice regarding quackery and hucksterism. The United States Federal Food, Drug, and Cosmetic Act and its amendments were reviewed, particularly as they pertain to dietary supplements and human growth hormone. Anti-aging quackery and hucksterism are pervasive on the Internet and in clinics advertising anti-aging treatments. Review of the marketing techniques of the industry revealed 15 common ruses used by many in the industry to market their products. Federal law states that distributing or administering human growth hormone for anti-aging or age-related problems is illegal. Nonetheless, anti-aging clinics thrive, administering human growth hormone to thousands of gullible and oftentimes vulnerable patients. Anti-aging quackery has become a multimillion dollar industry exacting great monetary, health, and social costs. Consumers and health care providers alike are wise to educate themselves on how to recognize quackery. Congress must reassess the wisdom of the 1994 Dietary Supplements Health and Education Act, which facilitates and, in numerous cases, endangers Americans on a grand scale. In the case of some substances such as human growth hormone, adequate legal safeguards are impotent without adequate resources allocated to enforcement agencies.

Aged↗
PubMed2004

Lower all-cause, cardiovascular, and cancer mortality in centenarians' offspring.

OBJECTIVES: To assess the cause of death for centenarians' offspring and controls. DESIGN: Cross-sectional study. SETTING: Community-based, nationwide sample. PARTICIPANTS: Family pedigree information was collected on 295 offspring of centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the centenarians but at least one of whom died at the average life expectancy. MEASUREMENTS: Age at death and cause of death. RESULTS: Centenarians' offspring had a 62% lower risk of all-cause mortality (P<.001), a 71% lower risk of cancer-specific mortality (P=.002), and an 85% lower risk of coronary heart disease-specific mortality (P<.001). Significant differences were not found for other causes of death. However of those who died centenarian offsprings dead at a significantly younger age than controls. CONCLUSION: These findings suggest that centenarians' offspring have lower all-cause mortality rates and cause-specific mortality rates for cancer and coronary heart disease. These results suggest that mechanisms for survival to exceptional old age may go beyond the avoidance or delay of cardiovascular disease and also include the avoidance or delay of cancer. Moreover survival advantage of centenarian offsprings may not be due to factors related to childhood mortality. Ultimately, survival to exceptional old age may involve lower susceptibility to a broad range of age-related diseases, perhaps secondary to inhibition of basic mechanisms of aging.

Adult↗
PubMed2004

Cardiovascular disease delay in centenarian offspring: role of heat shock proteins.

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P <.001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.

Aged↗
PubMed2003

Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan.

We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains approximately 50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy-Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity.

Adolescent↗
PubMed2003

Cardiovascular advantages among the offspring of centenarians.

BACKGROUND: A significant component of the ability to survive to exceptional old age may be familial. This study assessed the prevalence of age-related diseases in the offspring of centenarians. METHODS: The health histories of centenarian offspring (n=177) and controls (n=166) were assessed from 1997-2000 using a cross-sectional study design. The offspring of 192 centenarian subjects enrolled in the nationwide New England Centenarian Study were recruited and enrolled. Controls consisted of offspring whose parents were born in the same years as the centenarians but at least 1 of whom died at an average life expectancy. Prevalence of age-related diseases including heart disease, hypertension, diabetes, cancer, osteoporosis, stroke, dementia, cataracts, glaucoma, macular degeneration, depression, Parkinson's disease, thyroid disease, and chronic obstructive pulmonary disease were compared between the two groups. RESULTS: Centenarian offspring had a 56% reduced relative prevalence of heart disease (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.24, 0.80), a 66% reduced relative prevalence of hypertension (OR 0.34, 95% CI 0.21, 0.55), and 59% reduced relative prevalence of diabetes (OR 0.41, 95% CI 0.15, 1.12) after multivariate adjusted analyses. CONCLUSIONS: The offspring of centenarians demonstrate a markedly reduced prevalence of diseases associated with aging, in particular for cardiovascular disease and cardiovascular risk factors. Along with their parents, the centenarian offspring, who are in their 70s and 80s, may prove to be a valuable cohort to study genetic and environmental factors conducive to the ability to live to very old age in good health.

Aged↗
PubMed2002

Life-long sustained mortality advantage of siblings of centenarians.

Although survival to old age is known to have strong environmental and behavioral components, mortality differences between social groups tend to diminish or even disappear at older ages. Hypothesizing that surviving to extreme old age entails a substantial familial predisposition for longevity, we analyzed the pedigrees of 444 centenarian families in the United States. These pedigrees included 2,092 siblings of centenarians, whose survival was compared with 1900 birth cohort survival data from the U.S. Social Security Administration. Siblings of centenarians experienced a mortality advantage throughout their lives relative to the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half the national level; male siblings had a similar advantage at most ages, although diminished somewhat during adolescence and young adulthood. Relative survival probabilities for these siblings increase markedly at older ages, reflecting the cumulative effect of their mortality advantage throughout life. Compared with the U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely to attain age 100 themselves, while female siblings were at least 8 times as likely.

Adolescent↗
PubMed2002

Is there an antiaging medicine?

In spite of considerable hype to the contrary, there is no convincing evidence that currently existing so-called "antiaging" remedies promoted by a variety of companies and other organizations can slow aging or increase longevity in humans. Nevertheless, a variety of experiments with laboratory animals indicate that aging rates and life expectancy can be altered. Research going back to the 1930s has shown that caloric restriction (also called dietary restriction) extends life expectancy by 30-40% in experimental animals, presumably at least partially by delaying the occurrence of age-dependent diseases. Mutations that decrease production of insulin growth factor I in laboratory mammals, and those that decrease insulin-like signaling in nematodes and fruit flies, have increased life expectancy as well. Other general strategies that appear promising include interventions that reduce oxidative stress and/or increase resistance to stress; hormone and cell replacement therapies may also have value in dealing with specific age-related pathologies. This article reports the findings of a consensus workshop that discussed what is known about existing and future interventions to slow, stop, or reverse aging in animals, and how these might be applied to humans through future research.

Aging↗