Search PubMed⌕ Search

Biomedical subjects

L Hayflick

Publications and source records attributed to L Hayflick.

At least 37 records · Page 2Linked to original sources
PubMed1989

Antecedents of cell aging research.

Our observation that normal human and animal cells have a limited capacity to divide and function in vitro overturned a dogma held since the turn of the century. The dogma held that cultured normal cells are immortal and gerontologists interpreted this to mean that aging, therefore, could not be the result of intracellular events. We concluded that longevity and aging do result from intracellular events, and, in the subsequent 30 years, the validity of our finding has been widely confirmed. Other major findings have been made: (a) The number of population doublings and functional events that a cultured normal cell can undergo is inversely proportional to donor age and, probably, directly proportional to species longevity; (b) the limit on cell division and function also occurs in vivo when normal cells are transplanted seriatim; (c) as cell doublings or functional events reach their limit, changes occur in hundreds of variables from the molecular to the whole cell. Most importantly, many of these changes are identical to those seen in intact humans and animals as they age; (d) WI-38, the first widely distributed normal human cell strain has retained its memory of population doubling level during 27 years of cryogenic storage. This is the longest time that any normal human cell has ever been preserved. Evidence that longevity is determined by genetic events is overwhelming but evidence that age changes are the result of gene expression is not. Normal age changes must be distinguished from disease. Because few feral animals ever become old, natural selection could not have favored the development of a genetically programmed aging process. In the 2 or 3 million years of human existence, too few old humans existed to have provided a selective advantage favoring the development of a genetic program that would determine age changes. The selective advantage of maintaining physiological vigor for as long as possible in order to insure maximum reproductive success may be the essential indirect determinant of longevity. Natural selection has provided sexually mature animals with extraordinary reserve capacities in virtually all organs. After sexual maturation, animals continue to function by utilizing the reserve capacity that evolved to insure that they would attain reproductive success. The magnitude of reserve capacity is the essential element in determining postdevelopmental longevity. Thus "Why do we age?" may be the wrong question. The right question may be "Why do we live as long as we do?"

Cell Survival↗
PubMed1985

The cell biology of aging.

It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their failure to divide. Many of these functional decrements are identical to decrements found in humans as they age. Thus it is likely that these decrements are also the precursors of age changes in vivo. The finite replicative capacity of normal cells is never seen to occur in vivo because aging and death of the individual occurs well before the doubling limit is reached.

Aging↗
PubMed1984

Intracellular determinants of cell aging.

Several important findings have been made since our observation that normal human and animal cells have a finite capacity to replicate and function. Among these are that: an inverse relationship exists between donor age and population doubling potential; more than 100 functional increments and decrements occur in cultured normal human cells before they age and die; normal tissue transplanted seriatim in vivo reveals a finite replicative and functional capacity; a direct relationship may exist between species maximum lifespan and population doubling potential of their cultured fibroblasts; the latent period increases as a function of age; cells from patients with accelerated aging syndromes undergo fewer population doublings than do age matched controls; and cultured fibroblasts from longer lived species have greater DNA repair capacity than do cells from species with shorter lifespans. Efforts to determine the location of the intracellular chronometer that controls these events has shown that the chronometer is intranuclear. The phenomenon of senescence has been found to be dominant over immortality.

Aging↗