Thomas T. Perls, MD, MPH, FACP

Professor, Medicine

Thomas Perls
(617) 638-6670
72 E. Concord St Robinson (B)

Biography

Expertise in epidemiology, genetics of aging and exceptional longevity.

Dr. Perls is among the international leaders in the field of human exceptional longevity. He has been responsible for numerous novel and pivotal findings in the field:

• Intact cognitive function amongst centenarians may be a function of demographic selection in which younger elderly with poor function die off leaving behind a select group of survivors with lower relative risk for common causes of cognitive impairment such as Alzheimer’s disease.

• Twenty percent of female centenarians had children after the age of 40 compared with 5% of women from their birth cohort. The results suggest that women who had children after the age of 40 had a 4 times greater risk of living to 100 or older (Nature).

• Delayed age of menopause and therefore the ability to have more children may be an important genetic selective pressure to evolve genetic variants that slow aging and decrease risk for age related diseases.

• Relative to octogenarians and nonagenarians, Alzheimer’s becomes less common amongst centenarians while rarer causes of neuropathology become more common, suggesting that centenarians have a relative resistance to Alzheimer’s, which also correlates with the decreased frequency of the apolipoprotein E-4 allele amongst Caucasian centenarians.

• The first to report a series of families that demonstrate remarkable clustering for exceptional longevity (J Amer Geriatrics Society).

• Siblings of centenarians have markedly increased risks for survival to 100 relative to their birth cohort (Lancet and PNAS).

• The children of centenarians have approximately 60% reduced rates of heart disease, stroke, diabetes and hypertension and 80% reduced overall mortality in their early seventies compared to their average birth cohort.

• A substantial proportion of centenarians live with age-related diseases usually associated with significant mortality, for more than 20 years (40%, called survivors), another group have such diseases after the age of 80 (45%, called delayers) and then there are about 15% of centenarians who have none of these diseases at the age of 100 (called escapers). Despite this, more than 90% of centenarians are functionally independent in their early nineties.

• At even older ages however, semi-super-centenarians (ages 105-109 years) and even more so, supercentenarians (age 110+), usually delay such age related diseases towards the ends of their lives. The supercentenarians particularly do this, experiencing such diseases on average in the last 5% of their extremely long lives (J Gerontology, 2012). These findings support for the first time Jim Fries’ “compression of morbidity” hypothesis that he proposed in his 1980 New England Journal of Medicine article. The observed homogeneity of this age group in terms of the delay or escape of these diseases is consistent with their being the extreme tail of the population and that they are more likely to have genetic factors in common that confer such an extreme survival advantage.

• Dr. Perls, working with a wide range of disciplines including statisticians, geneticists and computer scientists, has led the production of a landmark article in which a genetic model consisting of 281 genetic markers predicts with 85% accuracy whom in their sample of controls and centenarians is age 105+ years (published this January in PLoS ONE). The accuracy of the model is lower, about 60% for nonagenarians and centenarians at age 100, which supports the hypothesis that the genetic component of survival to older and older age beyond 100 gets progressively stringer. The authors made some additionally important findings: the centenarians have just as many disease-associated genetic variants as people dying at younger ages. Presumably, centenarians are able to survive to much older ages in part because of the presence of longevity associated variants that counter the effects of such disease variants. Particularly for the oldest subjects in the study, most of these 281 markers presumably point to such longevity associated variants, including genes already well known in the biology of aging community such as the Werner’s gene, Lamin A (Hutchison Guildford Syndrome) and super oxide dismutase. It’s very interesting that there are variants for genes known to cause premature aging that may have the opposite effect and contribute to exceptional longevity.

• In part in order to search for functional variants associated with the SNPs noted in the above model, Dr. Perls also led an effort to whole genome sequence, for the first time, not just one centenarian, but two supercentenarians, a man and woman, both over the age of 114 years (Frontiers in Genetics, January 2012).

Other Positions

  • Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
  • Active Staff Privileges, Medicine, Boston Medical Center

Education

  • University of Rochester, MD
  • Pitzer College, BA
  • Harvard School of Public Health, MPH

Classes Taught

Publications

  • Published on 6/1/2015

    Villa F, Carrizzo A, Spinelli CC, Ferrario A, Malovini A, Maciag A, Damato A, Auricchio A, Spinetti G, Sangalli E, Dang Z, Madonna M, Ambrosio M, Sitia L, Bigini P, Calì G, Schreiber S, Perls T, Fucile S, Mulas F, Nebel A, Bellazzi R, Madeddu P, Vecchione C, Puca AA. Genetic Analysis Reveals a Longevity-Associated Protein Modulating Endothelial Function and Angiogenesis. Circ Res. 2015 Jul 31; 117(4):333-45.

    Read at: PubMed
  • Published on 3/24/2015

    Perls T, Handelsman DJ. Disease mongering of age-associated declines in testosterone and growth hormone levels. J Am Geriatr Soc. 2015 Apr; 63(4):809-11.

    Read at: PubMed
  • Published on 3/10/2015

    Minster RL, Sanders JL, Singh J, Kammerer CM, Barmada MM, Matteini AM, Zhang Q, Wojczynski MK, Daw EW, Brody JA, Arnold AM, Lunetta KL, Murabito JM, Christensen K, Perls TT, Province MA, Newman AB. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index. J Gerontol A Biol Sci Med Sci. 2015 Aug; 70(8):1003-8.

    Read at: PubMed
  • Published on 3/5/2015

    Ash AS, Kroll-Desrosiers AR, Hoaglin DC, Christensen K, Fang H, Perls TT. Are Members of Long-Lived Families Healthier Than Their Equally Long-Lived Peers? Evidence From the Long Life Family Study. J Gerontol A Biol Sci Med Sci. 2015 Aug; 70(8):971-6.

    Read at: PubMed
  • Published on 2/1/2015

    Stevenson M, Bae H, Schupf N, Andersen S, Zhang Q, Perls T, Sebastiani P. Burden of disease variants in participants of the long life family study. Aging (Albany NY). 2015 Feb; 7(2):123-32.

    Read at: PubMed
  • Published on 1/1/2015

    Sun F, Sebastiani P, Schupf N, Bae H, Andersen SL, McIntosh A, Abel H, Elo IT, Perls TT. Extended maternal age at birth of last child and women''s longevity in the Long Life Family Study. Menopause. 2015 Jan; 22(1):26-31.

    Read at: PubMed
  • Published on 12/1/2014

    Barral S, Cosentino S, Christensen K, Newman AB, Perls TT, Province MA, Mayeux R. Common genetic variants on 6q24 associated with exceptional episodic memory performance in the elderly. JAMA Neurol. 2014 Dec 1; 71(12):1514-9.

    Read at: PubMed
  • Published on 11/18/2014

    Bae HT, Perls TT, Sebastiani P. An efficient technique for Bayesian modeling of family data using the BUGS software. Front Genet. 2014; 5:390.

    Read at: PubMed
  • Published on 9/8/2014

    Broer L, Buchman AS, Deelen J, Evans DS, Faul JD, Lunetta KL, Sebastiani P, Smith JA, Smith AV, Tanaka T, Yu L, Arnold AM, Aspelund T, Benjamin EJ, De Jager PL, Eirkisdottir G, Evans DA, Garcia ME, Hofman A, Kaplan RC, Kardia SL, Kiel DP, Oostra BA, Orwoll ES, Parimi N, Psaty BM, Rivadeneira F, Rotter JI, Seshadri S, Singleton A, Tiemeier H, Uitterlinden AG, Zhao W, Bandinelli S, Bennett DA, Ferrucci L, Gudnason V, Harris TB, Karasik D, Launer LJ, Perls TT, Slagboom PE, Tranah GJ, Weir DR, Newman AB, van Duijn CM, Murabito JM. GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 Candidacy. J Gerontol A Biol Sci Med Sci. 2015 Jan; 70(1):110-8.

    Read at: PubMed
  • Published on 6/2/2014

    Kaufman LB, Setiono TK, Doros G, Andersen S, Silliman RA, Friedman PK, Perls TT. An oral health study of centenarians and children of centenarians. J Am Geriatr Soc. 2014 Jun; 62(6):1168-73.

    Read at: PubMed

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