Aging and Sex, DNA Repair in
77
indicated in Table 2, excess MGMT results
in decreased aging (life span extension).
2.6
Enzymes of DNA Repair Pathways and
Enzymes Regulating DNA
Damage–inducing ROS Contribute to
Determination of Aging
Eleven
speciFc
DNA
repair
enzymes
distributed
among
NER,
BER,
HRR,
NHEJ and MGMT were found to in-
crease lifespan when elevated or decrease
life span when defective (Tables 2 and
3). In addition, alterations of four en-
zymes causing reduced levels of DNA-
damaging ROS (increases of Cu/ZnSOD,
MnSOD or catalase, or loss of p66Shc)
also increase life span. These Fndings
strongly support the DNA damage theory
of aging.
3
The DNA Repair (and Complementation)
Theory of Sex
3.1
Meiosis, an Adaptation for Repairing Germ
Line DNA
It is useful for further discussion to de-
Fne sexual reproduction and to clarify
its key components. Such a deFnition,
to be general, should encompass sexual
processes in all organisms, both eukary-
otes and prokaryotes.
Sexual reproduction
is the process by which genetic material
(usually DNA) from two separate parents
is brought together in a common cytoplasm
where recombination of the genetic material
ordinarily occurs, followed by the passage
of the recombined genome(s) to progeny
.
Thus, sexual reproduction has two basic
elements: (1) recombination, in the sense
of the exchange of genetic material be-
tween two homologous chromosomes,
and (2) outcrossing, in the sense that
the homologous chromosomes from two
different individuals come together in the
same cell.
In eukaryotes, the germ line is the
cellular lineage that connects successive
meioses. The germ line is a key fea-
ture of sexual reproduction. In obligate
sexual organisms such as humans, the
germ line is potentially immortal (see
Section 1.9) in contrast with the somatic
line. This feature of the germ line pre-
sumably is due to adaptations present
in the germ line that are lacking in
the somatic line. Meiosis is a process
unique to the germ line, and it ap-
pears to be an adaptation speciFcally for
promoting recombinational repair (HRR),
since a major characteristic of meio-
sis is the close pairing of homologous
chromosomes.
Some diploid organisms form gametes
(such as sperm and egg cells) by meio-
sis, but then undergo self-fertilization or
automixis (a process in which two hap-
loid products of meiosis fuse to form
a diploid zygote). Such processes are
c
omm
o
ni
np
l
a
n
t
sa
n
di
n
v
e
r
t
e
b
r
a
t
e
s
.
Self-fertilization and automixis are not
strictly sexual processes since they lack
the outcrossing feature of sex. How-
ever, many of the organisms that un-
dergo these asexual processes are also
facultatively sexual. In the following dis-
cussion, we assume that meiosis serves
essentially the same function in all or-
ganisms in which it occurs and that the
germ line in facultative or obligate self-
fertilizing and automictic eukaryotes is
the cell lineage that connects successive
meioses.
previous page 77 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 79 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off