"#$%&'( )*+#$,-.

/0($12 32#1%4 #-5 "6%-2((7

8.6-.
WPC Classlcauon lll
MusculoskeleLal (MSk) ulsorders: Aglng
Cverall/1rend:
1he decllne ls
chronlc/perslsLenL
and may lead Lo
resLrlcuons ln
movemenLs.
1he raLe and
magnlLude of
changes are
modlable buL Lhe
eecL ls noL
reverslble
Lowerlng Lhe 8lsk for Chronlc luncuonal
LlmlLauons [!"#$$ &' ($) *++, -.../
MalnLalnlng or
lmprovlng
muscular sLrengLh
laLer ln llfe
reduces Lhe
percenLage of
funcuonal
llmlLauons by over
30 for boLh men
and women
Muscle SLrengLh As A redlcLor Cf Cld Age ulsablllLy
0(1'(1&1 &' ($) 23*3 4555
Muscle SLrengLh As A redlcLor Cf Cld Age ulsablllLy
0(1'(1&1 &' ($) 23*3 4555
6&78$& 9#': ;"&('&" <=>?$&
>'"&1;': @="#1; <#@$#A& ("& (' (
$79&" "#>B 7A C&?7<#1; @#>(C$&@
C&?(=>& 7A ':&#" ;"&('&" "&>&"D& 7A
>'"&1;': "&;("@$&>> 7A ?:"71#?
?71@#E71> ':(' <(F @&D&$78)
uecreaslng SkeleLal Muscle
Mass and SLrengLh wlLh Aglng
oLenual Causes - (sull belng ldenued)
l. Loss of hormonal adapLauons (decrease ln
LesLosLerone and growLh hormone)
ll. Loss of neurologlcal lnuences (selecuve loss
of Lype ll moLor unlLs resulung ln clusLer of
1ype l muscle bers wlLh age)
lll. rogrammed Cell ueaLh - 9#'$&+2-6#
paLhways
Caspases (enzymes LhaL breakdown and degrade
proLelns and unA), and
ApopLosls-lnduclng lacLor (All) (modled nucleus)
uecreaslng Muscle SLrengLh wlLh Aglng
Sarcopenla assoclaLed wlLh ApopLosls
CharacLerlzed by :
unA breaklng up/unA fragmenLauon,
Caspases (enzymes LhaL breakdown and degrade
unA and proLelns),
nucleus dlsassembly/deLerlorauon (nuclear
condensauon)
ApopLosls-lnduclng lacLor (All) (from mlLochondrla)
uecreaslng Muscle SLrengLh wlLh Aglng
8+&+%&,$ :#%4;#<( Lead Lo rogrammed Cell ueaLh:

caspases procaspases
lnacuve Acuve
unA

roLeln
lnluaLor Caspases
Caspase-8, -10
Caspase-9,
Caspase-12
LecLor Caspases
Caspase-3,
Caspase-6, -7
Acuvauon:
lncreased [calclum] - caspase-12, (perhaps -8, and -10)
lncreased 8CS - caspase-8, -10
8eleased from mlLochondrla - ApopLosome, caspase-9
uecreaslng Muscle SLrengLh wlLh Aglng
oLenual Causes of Sarcopenla - (sull belng ldenued)
Acuvauon of proLeolyuc paLhways - proLeases
(enzymes LhaL breakdown and degrade proLelns) by:
l. Caspase-dependenL
(prevlous sllde)
ll. Caspase-lndependenL
MlLochondrlal dysfuncuon - leads Lo apopLosls-
lnduclng facLor (All) - resulLs ln nuclear
condensauon
uecreaslng Muscle SLrengLh wlLh Aglng
Sarcopenla ls Lhe loss of muscle mass and sLrengLh
due Lo aglng process
~1-2 muscle mass per year pasL 30yrs of age
loss of sLrengLh varles, may be greaLer percenL Lhen loss ln
muscle
revalence
lmpacLs 10-23 of Lhe populauon under 70yrs of age and
~40 above 80yrs of age (hypoplasla of 1ype ll muscle
bers)
Concerns
8lsk of funcuonal llmlLauons - (revlewed earller)
uecreaslng Muscle SLrengLh wlLh Aglng
lmpacL of 1ralnlng (sLrengLh and endurance) on
ApopLouc aLhways ln Lhe Llderly

lmproved calclum handllng - Lherefore noL as much
accumulauon
lmproved mlLochondlal funcuon
uecreased levels of apopLosome
8educed All

uecreaslng Muscle SLrengLh wlLh Aglng
8+&+%&,$ :#%4;#<( Lead Lo rogrammed Cell ueaLh:

caspases procaspases
lnacuve Acuve
unA

roLeln
=#(+#(2>?2+2-52-% :'&$2((2(
uecreaslng Muscle SLrengLh wlLh Aglng
8+&+%&,$ :#%4;#<( Lead Lo rogrammed Cell ueaLh:

caspases procaspases
lnacuve Acuve
unA

roLeln
Acuvauon:
lncreased [calclum] ln muscle - leaky sarcoplasmlc reuculum
lncreased 8eacuve Cxygen Specles (8CS) from mlLochondrla
8eleased cyLochrome c from a leaky mlLochondrla
uecreaslng Muscle SLrengLh wlLh Aglng
8+&+%&,$ :#%4;#<( Lead Lo rogrammed Cell ueaLh:

caspases procaspases
lnacuve Acuve
unA

roLeln
lnluaLor Caspases
Caspase-8, -10
Caspase-9,
Caspase-12
LecLor Caspases
Caspase-3,
Caspase-6, -7
uecreaslng Muscle SLrengLh wlLh Aglng
8+&+%&,$ :#%4;#<( Lead Lo rogrammed Cell ueaLh:

caspases procaspases
lnacuve Acuve
unA

roLeln
lnluaLor Caspases
Caspase-8, -10
Caspase-9,
Caspase-12
LecLor Caspases
Caspase-3,
Caspase-6, -7
Acuvauon:
lncreased [calclum] - caspase-12, (perhaps -8, and -10)
lncreased 8CS - caspase-8, -10
8eleased cyLochrome c -Apaf1-A1 (ApopLosome) - caspase-9
-@#A #-5 @$1>B '2.01#%2 $<%&$4>$ '212#(2
nuclear Condensauon or ulsassembly
All
AIF (Apoptosis-inducing Factor)
unA lragmenLauon