Ageing, Growth And Death

In 1974, I published a paper in Nature on the ageing growth and death of cells in which I put forward a new hypothesis that accounts for many of the facts of cellular senescence and regeneration in plants and in animals. In essence, I proposed that harmful breakdown products build up in cells as they age, and that cells can be regenerated by asymmetric cell division so that one of the cells receives more of these harmful products. Thus one daughter cell will pay the price of mortality while the other is rejuvenated. This kind of asymmetric division takes place in the growing regions of plants, the meristems, and in stem cells in animals. It also occurs in the formation of egg cells in plants and animals. In both cases, the meiotic division of the egg mother cell results in one supremely regenerated cell, the egg cell, and three other cells which soon die. In animals these very mortal sisters of the egg cell are called polar bodies.

Cellular Senescence, Rejuvenation and Potential Immortality

Proceedings of the Royal Society B (2022), 289, 20212434
https://doi.org/10.1098/rspb.2021.2434
by Rupert Sheldrake

Abstract

Ageing, death, and potential immortality lie at the heart of biology, but two seemingly incompatible paradigms coexist in different research communities and have done since the nineteenth century. The universal senescence paradigm sees senescence as inevitable in all cells. Damage accumulates. The potential immortality paradigm sees some cells as potentially immortal, especially unicellular organisms, germ cells and cancerous cells. Recent research with animal cells, yeasts and bacteria show that damaged cell constituents do in fact build up, but can be diluted by growth and cell division, especially by asymmetric cell division. By contrast, mammalian embryonic stem cells and many cancerous and ‘immortalized’ cell lines divide symmetrically, and yet replicate indefinitely. How do they acquire their potential immortality? I suggest they are rejuvenated by excreting damaged cell constituents in extracellular vesicles. If so, our understanding of cellular senescence, rejuvenation and potential immortality could be brought together in a new synthesis, which I call the cellular rejuvenation hypothesis: damaged cell constituents build up in all cells, but cells can be rejuvenated either by growth and cell division or, in ‘immortal’ cell lines, by excreting damaged cell constituents. In electronic supplementary material, appendix, I outline nine ways in which this hypothesis could be tested.

The Ageing, Growth and Death of Cells

Nature, Vol. 250, No. 5465, pp. 381-385, August 2nd 1974
by Rupert Sheldrake

Abstract

The ageing and death of cells in higher plants and higher animals are discussed in relation to cellular rejuvenation by growth and division. The full text article is available for download in the the following formats.

Death

Theoria to Theory 7, 31-38 (1973)
by Rupert Sheldrake

Abstract

Death is out of fashion, rarely discussed forgotten as much as it can be. It is too close to us all. But however much or little we may choose to think about our own inevitable mortality, death is a fact of life which must be considered by any science of life. But even within biology death has been more or less ignored. I think that this has imposed a great limitation on our understanding of life itself.

Cell Differentiation in Plants

As cells in plants turn into wood cells, called xylem cells, they thicken up their walls, and then the cell contents die and dissolve. The developing xylem cells also dissolve away their end walls, so that the dead, empty cells form tiny tubes through which the sap flow from the roots to the shoots. It seemed to me very likely that as new xylem cells formed and became part of the water-conducting system, the contents of the self-digested cells would be flushed away with the sap, and be carried upwards in it. I analysed the sap from several species of plants to see if it did contain breakdown products and enzymes of the kind likely to be involved in the autolysis, or self-digestion, of the differentiating xylem cells, and found that indeed it did. See Some Constituents of Xylem Sap and their Possible Relationship to Xylem Differentiation

Cellulase and Cell Differentiation in Acer pseudoplantanus

Planta (1970) 95, 167-178 1-13
https://doi.org/10.1007/BF00387248
by Rupert Sheldrake

Abstract

Homogenates of differentiating xylem and phloem tissue have higher cellulase activities than cambial samples; the highest activity is always found in phloem. Callus tissue, in which no vascular differentiation occurs, contains only low cellulase activity. The results suggest that cellulase is involved in vascular differentiation.

Different pH optima of cellulase activity were found: in cambium, xylem and phloem tissue, cellulase activity with an optimum at about pH 5.9 is predominantly membrane-bound; it is sedimentable at 100,000 g and releasable by Triton X-100. The same may be true of activity with an optimum at pH 5.3. Phloem tissue also contains a soluble, cytoplasmic cellulase of high activity at pH 7.1 and xylem tissue contains cytoplasmic cellulase with an optimum at pH 6.5. Low cellulase activity with a pH optimum similar to that of xylem homogenates was found in xylem sap. Cellulase activity in abscission zones increases greatly just before leaf abscission. Abscission zone cellulase has two pH optima, et 5.3 and 5.9; both activities are increased by Triton treatment of homogenates. The possible existence of several different cellulases forming part of a cellulase complex, and the role of the enzymes in hydrolysing wall material during cell differentiation are discussed.

A Cellulase in Hevea Latex

Physiologia Plantarum (1970), 23, 267-77
https://doi.org/10.1111/J.1399-3054.1970.TB06416.X
by Rupert Sheldrake, G.F.J. Moir

Abstract

Using a viscometric method of the latex of Hevea brasiliensis was found to contain a highly active cellulase capable of hydrolysing carboxymethyl cellulose. The enzyme has a pH optimum of around 6.3. It is present in the serum of the latex and is not membrane-bound to any significant extent. Similar cellulase activities were detected in latex from old and new latex vessel rings and also in latex from regularly tapped vessels and newly tapped vessels. The possible role of the enzyme in the removal of cell wall material during the differentiation of latex vessels is discussed.

Cellulase in Latex and its Possible Significance in Cell Differentiation

Planta (Berl.), (1969), 89, 82-4
https://doi.org/10.1007/BF00386498
by Rupert Sheldrake

Abstract

Cellulase was found to be present in the latex of species with articulated laticifers but it could not be detected in the latex of species with non-articulated laticifers. It is suggested that cellulase is involved in the removal of end walls during the differentiation of articulated laticifers.

Some Constituents of Xylem Sap and their Possible Relationship to Xylem Differentiation

Journal of Experimental Botany, (November 1968), 19 (61), 681-9
https://doi.org/10.1093/JXB%2F19.4.681
by Rupert Sheldrake and D.H. Northcote

Abstract

Bleeding sap of Actinidia chinensis and Betula populifolia and guttation fluid of Avena sativa were analysed for sugars, amino-acids, auxin, and certain enzymes. A wide range of amino-acids was found in all three. Auxin was not detected in the bleeding sap, but was present in Avena guttation fluid (5.1 ug IAA equivalent/1). 'IAA oxidase', acid phosphatase, ribonuclease, deoxyribonuclease, and protease were detected in the bleeding sap and guttation fluid. The possibility that some of the substances found in sap and guttation fluid are products of autolysing, differentiating xylem cells in the roots is discussed.