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Cited by 418Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceEvolution and Genetic Dynamics

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Biological Aging Is No Longer an Unsolved Problem

HAYFLICK, LEONARD·2007·Annals of the New York Academy of Sciences
DOI 10.1196/annals.1395.001
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Abstract

Abstract: The belief that aging is still an unsolved problem in biology is no longer true. Of the two major classes of theories, the one class that is tenable is derivative of a single common denominator that results in only one fundamental theory of aging. In order to address this complex subject, it is necessary to first define the four phenomena that characterize the finitude of life. These phenomena are aging, the determinants of longevity, age‐associated diseases, and death. There are only two fundamental ways in which age changes can occur. Aging occurs either as the result of a purposeful program driven by genes or by events that are not guided by a program but are stochastic or random, accidental events. The weight of evidence indicates that genes do not drive the aging process but the general loss of molecular fidelity does. Potential longevity is determined by the energetics of all molecules present at and after the time of reproductive maturation. Thus, every molecule, including those that compose the machinery involved in turnover, replacement, and repair, becomes the substrate that experiences the thermodynamic instability characteristic of the aging process. However, the determinants of the fidelity of all molecules produced before and after reproductive maturity are the determinants of longevity. This process is governed by the genome. Aging does not happen in a vacuum. Aging must be the result of changes that occur in molecules that have existed at one time with no age changes. It is the state of these pre‐existing molecules that governs longevity determination. The distinction between the aging process and age‐associated disease is not only based on the molecular definition of aging described above but it is also rooted in several practical observations. Unlike any disease, age changes (a) occur in every multicellular animal that reaches a fixed size at reproductive maturity, (b) cross virtually all species barriers, (c) occur in all members of a species only after the age of reproductive maturation, (d) occur in all animals removed from the wild and protected by humans even when that species probably has not experienced aging for thousands or even millions of years, (e) occur in virtually all animate and inanimate matter, and (f) have the same universal molecular etiology, that is, thermodynamic instability. Unlike aging, there is no disease or pathology that shares these six qualities. Because this critical distinction is poorly understood, there is a continuing belief that the resolution of age‐associated diseases will advance our understanding of the fundamental aging process. It will not. The distinction between disease and aging is also critical for establishing science policy because although policy makers understand that the funding of research on age‐associated diseases is an unquestioned good, they also must understand that the resolution of age‐associated diseases will not provide insights into understanding the fundamental biology of age changes. They often believe that it will and base decisions on that misunderstanding. The impact has been to fund research on age‐associated diseases at several orders of magnitude greater than what is available for research on the biology of aging. There is an almost universal belief by geriatricians and others that the greatest risk factor for all of the leading causes of death is old age. Why then are we not devoting significantly greater resources to understanding more about the greatest risk factor for every age‐associated pathology by attempting to answer this fundamental question—“What changes occur in biomolecules that lead to the manifestations of aging at higher orders of complexity and then increase vulnerability to all age‐associated pathology?”

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Crossref · 10.1196/annals.1395.001

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Research works printed but not linked: 1

  1. Anderson R.N., 1999, Decennial Life Tables for 1989–1991, Vol. 1, No. 4. United States life tables eliminating certain causes of death

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Metadata

Authors
HAYFLICK, L.
Affiliations
University of California, San Francisco (US)
Corresponding author
HAYFLICK, LEONARD
ORCID
HAYFLICK, LEONARD
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2007-04
Volume
1100
Issue
1
Pages
1-13
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1196/annals.1395.001
OpenAlex
W2156815362
Cited by
418
References
14
Citations by year
2026: 16 · 2025: 19 · 2024: 18 · 2023: 16 · 2022: 33 · 2021: 25 · 2020: 20 · 2019: 21 · 2018: 27 · 2017: 27 · 2016: 18 · 2015: 25 · 2014: 18 · 2013: 23 · 2012: 19
FWCI
6.00
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 17 d)
Locations
  • Annals of the New York Academy of Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
aging, thermodynamic instability, age-related diseases, programmed aging, stochastic aging, reproductive maturation, science policy, death
MeSH terms
Adult, Aged, Aging, Animals, Humans, Life Expectancy, Longevity, Middle Aged, Models, Biological

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