Exhibit 10.10  AMENDED AND RESTATED EMPLOYMENT AGREEMENT  THIS AMENDED AND
RESTATED EMPLOYMENT AGREEMENT dated as of January 3, 2008 (the Agreement)
is by and between Sirtris Pharmaceuticals, Inc. (the Company), a Delaware
corporation with its principal place of business at 200 Technology Square,
Cambridge, Massachusetts, and Christoph Westphal (the Executive).  WHEREAS, the
Company and the Executive are parties to a certain Employment Agreement dated February 14,
2005 and as amended on August 30, 2006 and February 13, 2007
(collectively, the Previous Agreement) pursuant to which the Executive has
been serving the Company as its President and Chief Executive Officer; and  WHEREAS, the
Company and the Executive desire to make certain changes to the terms and
conditions of the Executives employment;  NOW, THEREFORE, in
consideration of the mutual covenants and promises contained herein and other
good and valuable consideration, the receipt and sufficiency of which are
hereby acknowledged, the Company offers and the Executive accepts employment
upon the following amended and restated terms and conditions:  1.Position and Duties.  (a)The Company.Upon the terms and subject to the
conditions set forth in this Agreement, the Company hereby offers and the
Executive hereby accepts employment with the Company to serve as its President
and Chief Executive Officer, subject to the direction and control of the Board
of Directors of the Company (the Board). 
In addition, the Executive will serve without further compensation as a
member of the Board for so long as the Executive serves as the Companys Chief
Executive Officer, and will serve as the Vice Chairman of the Board until the
Board determines otherwise.  The
Executive agrees to perform the duties of his position and such other duties as
reasonably may be assigned to him from time to time.  The Executive also agrees that while employed
by the Company, except as provided in Section 1(b) below, he will
devote his full business time and his best efforts, business judgment, skill
and knowledge exclusively to the advancement of the business and interests of
the Company and to the discharge of his duties and responsibilities for it.  (b)           Activities Outside the
Company.The Executive may
have four outside commitments with companies other than the Company (including
service as a member of the board of directors or as an advisor of such other
companies), with such outside commitments to be subject to the approval of the
Companys Nominating and Corporate Governance Committee (the Committee).  The Committee may also, in its discretion,
increase the number of outside commitments the Executive may have.  The Executive will notify the Committee of
any change in his outside commitments. 
The Executive will, as a general rule, not attend board meetings of any
other company other than the Company and those other companies for which he serves
as a director.


2.Compensation and Benefits.During the Executives employment,
as compensation for all services performed by the Executive for the Company and
subject to his performance of his duties and responsibilities for the Company,
pursuant to this Agreement or otherwise, the Company will provide the Executive
the following pay and benefits:  (a)           Base Salary.   From
the period of the date hereof until December 31, 2008, the Company will
pay the Executive a base salary at the rate of Four Hundred Fifty Thousand
Dollars ($450,000) per year, payable in accordance with the regular payroll
practices of the Company for its executives, as in effect from time to time,
and subject to increase from time to time by the Board in its discretion.  (b)           Bonus Compensation.  The Executive shall be considered annually by
the Board for a bonus with a target of 60% of the Base Salary earned, which
percentage shall be subject to adjustment from time to time by the Board in its
discretion.  The amount of the bonus
shall be determined by the Board, based on its assessment, in its discretion,
of the Executives performance and that of the Company against appropriate
goals established annually by the Company after consultation with the
Executive.Any bonus due to the
Executive hereunder will be payable not later than two and one-half months
following the close of the Companys fiscal year or the close of the calendar
year, if later, in which occurs the later of the two following dates:  (i) the date on which the Executive
first has a legally binding right (whether or not vested) to the bonus; and (ii) if
the Executives right to the bonus is subject to one or more vesting
conditions, the first date on which the Executives right to the bonus is no
longer subject to any substantial risk of forfeiture.  The foregoing rules shall be construed
and applied to ensure that any bonus payable to the Executive qualifies as a short-term
deferral under Section 409A of the Internal Revenue Code, as amended
(including the regulations thereunder, Section 409A).  Without limiting the generality of the
foregoing, for purposes of these rules the terms legally binding right
and substantial risk of forfeiture shall have the meaning assigned to them
under Treas. Regs. § 1.409A-1(b)(1) and § 1.409A-1(d),
respectively.  (c)           Restricted Common Stock.  The Company previously sold to the Executive
on February 14, 2005, pursuant to the Previous Agreement, 2,000,000 shares
of the restricted common stock of the Company at a purchase price of $0.001 per
share (the Restricted Shares), pursuant to the Stock Restriction Agreement by
and between the Company and the Executive dated February 14, 2005 and
subject to all terms thereof.  The
Restricted Shares shall continue to vest on the schedule set forth in the
Previous Agreement, restated here as follows: 400,000 of the Restricted Shares vested
as of February 14, 2005 and of the remaining 1,600,000 of the Restricted
Shares (the Remainder Shares), twenty-five percent (25%) of the Remainder
Shares vested on January 1, 2006 and the remainder of the Remainder Shares
shall vest ratably, on a quarterly basis, on the last date of each of the next
twelve (12) quarters thereafter, provided that the Executive remains in the
Companys employ at each such vesting date.  The Restricted
Shares and all other restricted stock and options granted to the Executive by
the Company shall be subject to any applicable stock option plan, stock
certificate and shareholder and/or option holder and restricted stock
agreements and other restrictions and limitations generally applicable to
equity held by Company executives or otherwise required by  2


law.  The Executive shall not be eligible to
receive any stock options, restricted stock or other equity of the Company,
however, whether under an equity incentive plan or otherwise, except as
expressly provided in this Agreement or as otherwise expressly authorized for
him individually by the Board. Further, prior to issuing the Restricted Shares
or any other stock options to the Executive, the Company may require that the
Executive provide such representations regarding the Executives sophistication
and investment intent and other such matters as the Company may reasonably
request.  (d)           Participation in Employee Benefit Plans.  The Executive will be entitled to participate
in all Employee Benefit Plans from time to time in effect for employees of the
Company generally, except to the extent such plans are duplicative of benefits
otherwise provided the Executive under this Agreement (e.g.,
severance pay) or under any other agreement. 
The Executives participation will be subject to the terms of the
applicable plan documents and generally applicable Company policies.  The Company may alter, modify, add to or
delete its Employee Benefit Plans at any time as it, in its sole judgment,
determines to be appropriate, without recourse by the Executive. For purposes
of this Agreement, Employee Benefit Plan shall have the meaning ascribed to
such term in Section 3(3) of ERISA, as amended from time to time.  (e)           Vacations.  The
Executive will be entitled to three weeks paid vacation (or such greater amount
as is generally made available to the Companys executive officers) in
accordance with the Companys policies from time to time in effect, in addition
to holidays observed by the Company. 
Vacation may be taken at such times and intervals as the Executive shall
determine, subject to the business needs of the Company, and otherwise shall be
subject to the policies of the Company, as in effect from time to time.  (f)            Business Expenses. 
The Company will pay or reimburse the Executive for all reasonable
business expenses incurred or paid by the Executive in the performance of his duties
and responsibilities for the Company, subject to any maximum annual limit and
other restrictions on such expenses set by the Company and to such reasonable
substantiation and documentation as it may specify from time to time.  Any such reimbursement that would constitute
nonqualified deferred compensation subject to Section 409A shall be
subject to the following additional rules: 
(i) no reimbursement of any such expense shall affect the Executives
right to reimbursement of any other such expense in any other taxable year; (ii) reimbursement
of the expense shall be made, if at all, not later than the end of the calendar
year following the calendar year in which the expense was incurred; and (iii) the
right to reimbursement shall not be subject to liquidation or exchange for any
other benefit.  3


3.Confidential Information, Non-Competition
and Proprietary Information.The
Executive has previously executed the Companys Confidentiality,
Non-Competition and Proprietary Information Agreement.   It is understood and agreed that breach by the
Executive of the Confidential Information, Non-Competition and Proprietary
Information Agreement shall constitute a material breach of this Agreement.  4.             Termination of Employment.  
The Executives employment under this Agreement shall continue until
terminated pursuant to this Section 4.  (a)           The
Company may terminate the Executives employment for Cause upon notice to the
Executive setting forth in reasonable detail the nature of the Cause.  The following, as determined by the Board in
its reasonable judgment, shall constitute Cause for termination:  (i) the Executives willful failure to
perform, or gross negligence in the performance of, his duties and
responsibilities to the Company and its Affiliates which is not remedied within
thirty (30) days of notice thereof; (ii) material breach by the Executive
of any material provision of this Agreement or any other agreement with the
Company or any of its Affiliates which is not remedied within thirty (30) days
of notice thereof; (iii) fraud, embezzlement or other dishonesty with
respect to the Company and any of its Affiliates, taken as a whole, which, in
the case of such other dishonesty, causes or could reasonably be expected to
cause material harm to the Company and any of its Affiliates, taken as a whole;
or (iv) the Executives conviction of a felony.  (b)           The
Company may terminate the Executives employment at any time other than for
Cause upon notice to the Executive.  (c)           The
Executive may terminate his employment hereunder for Good Reason by providing
notice to the Company of the condition giving rise to the Good Reason no later
than thirty (30) days following the occurrence of the condition, by giving the
Company thirty (30) days to remedy the condition and by terminating employment
for Good Reason within thirty (30) days thereafter if the Company fails to remedy
the condition.   For purposes of this
Agreement, Good Reason shall mean, without the Executives consent, the
occurrence of any one or more of the following events:  (i) material diminution in the nature or
scope of the Executives responsibilities, duties or authority, provided that
in the absence of a Change of Control none of the following shall constitute Good
Reason: (x) the Companys failure to continue the Executives appointment
or election as a director or officer of any of its Affiliates or (y) any
diminution in the nature or scope of the Executives responsibilities, duties
or authority that is reasonably related to a diminution of the business of the
Company or any of its Affiliates shall constitute Good Reason; (ii) any
diminution in position, base salary or bonus or in the nature or scope of the
Executives responsibilities, duties or authorityin
anticipation of or after a Change of Control, it being specifically
acknowledged that the Executives failure to continue as Chief Executive Officer
of the Company and to serve on the Board of Directors of the Company (and any
parent company directly or indirectly owning or controlling 50% or more of the
securities of the Company after the Change of Control) shall constitute Good
Reason; (iii) a reduction in the Executives base salary other than one
temporary reduction of not more than 120 days and not in excess of 20% of the
Executives base salary in connection with and in  4


proportion to a general reduction of the base salaries of the Companys
executive officers; (iv) failure of the Company to provide the Executive
the salary or benefits in accordance with Section 2 hereof after thirty
(30) days notice during which the Company does not cure such failure; or (v) relocation
of the Executives office more than thirty-five (35) miles from the location of
the Companys principal offices as of January 1, 2008.  (d)           The
Executive may terminate his employment with the Company other than for Good Reason
at any time upon one months notice to the Company.  (e)           This
Agreement shall automatically terminate in the event of the Executives death
during employment.  The Company may
terminate the Executives employment, upon notice to the Executive, in the event
the Executive becomes disabled during employment and, as a result, is unable to
continue to perform substantially all of his duties and responsibilities under
this Agreement for one-hundred and twenty (120) days during any period of three
hundred and sixty-five (365) consecutive calendar days.  If any question shall arise as to whether the
Executive is disabled to the extent that the Executive is unable to perform
substantially all of his duties and responsibilities for the Company and its
Affiliates, the Executive shall, at the Companys request and expense, submit
to a medical examination by a physician selected by the Company to whom the
Executive or the Executives guardian, if any, has no reasonable objection to
determine whether the Executive is so disabled and such determination shall for
the purposes of this Agreement be conclusive of the issue.  If such a question arises and the Executive
fails to submit to the requested medical examination, the Companys
determination of the issue shall be binding on the Executive.  5.             Severance Payments and Other
Matters Related to Termination.  (a)           Termination
pursuant to Section 4(b), 4(c), or 4(e).  Except as provided in Section 5(c) below,  (i) in the event of termination of the Executives
employment by the Company other than for Cause pursuant to Section 4(b) of
this Agreement or in the event of termination of the Executives employment by
the Executive for Good Reason pursuant to Section 4(c) of this
Agreement, (a) all unvested options and restricted stock which, by their
terms, vest only based on the passage of time (disregarding any acceleration of
the vesting of such options based on individual or Company performance) and
unvested Restricted Shares shall vest as of the date of termination
(notwithstanding anything to the contrary in Section 2(c) of this
Agreement) with respect to an additional one year of vesting (except that with
respect to restricted stock and the Restricted Shares, a minimum of 25% of such
unvested shares shall vest); and (b) the Company will continue to pay the
Executives base salary, at the rate in effect on the date of termination, for
a period of twelve (12) months from the date of termination and pay a pro-rata
portion (for the period from January 1 of the year of termination through
the date of termination) of the target cash bonus for the year in which the
Executive is terminated; or  (ii)  in the
event of the Executives termination of employment as a result of the Executives
death or disability at any time pursuant to Section 4(e) of the
Agreement, (a) all  5


unvested options and
restricted stock which, by their terms, vest only based on the passage of time (disregarding
any acceleration of the vesting of such options based on individual or Company
performance) and unvested Restricted Shares shall vest as of the date of
termination (notwithstanding anything to the contrary in Section 2(c) of
this Agreement) with respect to an additional one year of vesting (except that
with respect to restricted stock and the Restricted Shares, a minimum of 25% of
such unvested shares shall vest); (b) to the extent the Companys benefits
do not include disability insurance benefits that will continue the Executives
base salary at 100% of the amount of such base salary for the period of twelve
(12) months from the date of termination, the Company shall pay such amount at
the time that the Executives base salary would be otherwise paid as shall
equal the amount by which 100% of the Executives base salary exceeds the
disability insurance benefits, if any, actually paid to him; and (c) the
Company shall pay the Executive a pro-rata portion (for the period from January 1
of the year of termination through the date of termination) of the target cash bonus
for the year in which the Executive is terminated.  If the Executive is participating in the Companys group health plan
and/or dental plan at the time the Executives employment terminates (whether
such termination is as described in (i) or (ii) above), and the
Executive exercises his right to continue participation in those plans under
the federal law known as COBRA, or any successor law, the Company will pay or,
at its option, reimburse the Executive, for the full premium cost of that
participation for twelve (12) months following the date on which the Executives
employment with the Company terminates or, if earlier, until the date the
Executive becomes eligible to enroll in the health (or, if applicable, dental)
plan of a new employer.  The Company will
also pay the Executive on the date of termination any base salary earned but
not paid through the date of termination and pay for any vacation time accrued
but not used to that date.  In addition,
the Company will pay the Executive any bonus which has been awarded to the
Executive, but not yet paid on the date of termination of his employment.  Subject to the Companys discretion, the
portion of any of the Executives base salary to be paid pursuant to i(b) and
ii(b) above that does not constitute nonqualified deferred compensation
within the meaning of Section 409A, will either be paid in a lump sum or
in accordance with normal payroll practices. Any portion of any of the
Executives base salary to be paid pursuant to i(b) and ii(b) above
that constitutes nonqualified deferred compensation within the meaning of Section 409A
shall be paid in a lump sum.  Any obligation of the Company to provide the Executive severance
payments or other benefits under this Section 5(a) is conditioned on the
Executive signing an effective release of claims in the form provided by the
Company (the Employee Release) following the termination of the Executives
employment, which release shall not apply to (i) claims for
indemnification in the Executives capacity as an officer or director of the
Company under the Companys Certificate of Incorporation, By-laws or agreement,
if any, providing for director or officer indemnification, (ii) rights to
receive insurance payments under any policy maintained by the Company and (ii) rights
to receive retirement benefits that are accrued and fully vested at the time of
the Executives termination.  Any
severance payments to be made in the form of salary continuation pursuant to
the terms of this Agreement shall be payable in accordance with the normal
payroll practices of the Company, and will begin at the Companys next regular
payroll period following the effective date of the Employee Release, but shall
be retroactive to the date of termination.  6


The Executive agrees to provide the Company prompt notice of the
Executives eligibility to participate in the health plan and, if applicable,
dental plan of any employer.  The
Executive further agrees to repay any overpayment of health benefit premiums
made by the Company hereunder.  (b)           Termination
other than pursuant to Section 4(b), 4(c) or 4(e).  In the event of any termination of the
Executives employment, other than a termination by the Company other than for
Cause pursuant to Section 4(b) of this Agreement, a termination by the
Executive for Good Reason pursuant to Section 4(c) of this Agreement or
a termination as a result of the Executives death or disability pursuant to Section 4(e),
the Company shall have the right to repurchase any unvested Restricted Shares
for $.001 per share, and the Company will pay the Executive any base salary
earned but not paid through the date of termination and pay for any vacation
time accrued but not used to that date. 
In addition, the Company will pay the Executive any bonus which has been
awarded to the Executive, but not yet paid on the date of termination of the
Executives employment.  The Company
shall have no other obligation to the Executive under this Agreement.  (c)           Upon
a Change of Control.  (i)            If
a Change of Control (as defined in Section 6 hereof) occurs, all of the
Executives remaining unvested options and restricted stock which, by their
terms, vest only based on the passage of time (disregarding any acceleration of
the vesting of such options based on individual or Company performance) and Restricted
Shares shall fully vest, effective upon the consummation of such Change of
Control.  If, within one year following
such Change of Control or otherwise in connection with such Change of Control,
the Company or any successor thereto terminates the Executives employment
other than for Cause, or the Executive terminates his employment for Good
Reason, then, in lieu of any payments to the Executive or on the Executives
behalf under Section 5(a) hereof, (i) the Company shall pay,
within thirty (30) days of such termination, (x) a lump sum payment equal
to the Executives then-current annual base salary for a period of eighteen (18)
months; and (y) pay a pro-rata portion (for the period from January 1
of the year of termination through the date of termination) of the target cash
bonus for the year in which the Executive is terminated; and,  (ii)           The Company and the
Executive agree that in the event it shall be determined that any of the
payments or benefits received or to be received by the Executive in connection
with a Change of Control or the Executives termination from employment would
be subject to the excise tax imposed by Section 4999 of the Code, together
with any interest or penalties imposed with respect to such excise tax (the Excise
Tax), then the Executive shall be entitled to promptly receive from the
Company an additional lump sum cash payment (the Gross-Up Payment) in an
amount such that, after payment by the Executive of all taxes related to such
payments and benefits, including any income taxes and the Excise Tax imposed
upon the Gross-Up Payment, the Executive retains an amount of the Gross-Up
Payment equal to the Excise Tax imposed upon such payments and benefits.  7


(d)           Except for any right the Executive
may have under applicable law to continue participation in the Companys group
health and dental plans under COBRA, or any successor law, benefits shall
terminate in accordance with the terms of the applicable benefit plans based on
the date of termination of the Executives employment, without regard to any
continuation of base salary or other payment to the Executive following
termination.  (e)           Provisions of this Agreement shall
survive any termination if so provided in this Agreement or if necessary or
desirable to accomplish the purposes of other surviving provisions, including
without limitation the Executives obligations under Section 3 of this
Agreement and under the Confidentiality, Non-Competition and Proprietary
Information Agreement.  The obligation of
the Company to make payments to the Executive or on the Executives behalf
under Section 5 of this Agreement is expressly conditioned upon the
Executives continued full performance of the Executives obligations under Section 3
hereof, under the Confidentiality, Non-Competition and Proprietary Information
Agreement, and under any subsequent agreement between the Executive and the
Company or any of its Affiliates relating to confidentiality, non-competition,
proprietary information or the like.  6.             Definitions.For purposes of this agreement,
the following definitions apply:  Affiliates means
all persons and entities directly or indirectly controlling, controlled by or
under common control with the Company, where control may be by management
authority, equity interest or otherwise.  Change of Control
shall mean (i) the acquisition of beneficial ownership (as defined in Rule 13d-3
under the Exchange Act) directly or indirectly by any person (as such term is
used in Sections 13(d) and 14(d) of the Exchange Act), of securities
of the Company representing a majority or more of the combined voting power of
the Companys then outstanding securities, other than an acquisition of
securities for investment purposes pursuant to a bona fide financing of the
Company; (ii) a merger or consolidation of the Company with any other
corporation in which the holders of the voting securities of the Company prior
to the merger or consolidation do not own more than 50% of the total voting
securities of the surviving corporation; or (iii) the sale or disposition
by the Company of all or substantially all of the Companys assets other than a
sale or disposition of assets to an Affiliate of the Company or a holder of
securities of the Company.  Person means an
individual, a corporation, an association, a partnership, an estate, a trust
and any other entity or organization, other than the Company or any of its
Affiliates.  7.             Conflicting
Agreements. The Executive hereby represents and warrants that his signing
of this Agreement and the performance of his obligations under it will not
breach or be in conflict with any other agreement to which the Executive is a
party or is bound and that the Executive is not now subject to any covenants
against competition or similar covenants or any court order that could affect
the performance of the Executives obligations under this  8


Agreement.  The Executive agrees that he will not
disclose to or use on behalf of the Company any proprietary information of a
third party without that partys consent.  8.             Withholding;
Other Tax Matters.  Anything
to the contrary notwithstanding, (a) all payments required to be made by
the Company hereunder to Executive shall be subject to the withholding of such
amounts, if any, relating to tax and other payroll deductions as the Company
may reasonably determine it should withhold pursuant to any applicable law or
regulation, and (b) to the extent any payment hereunder shall be required
to be delayed until six months following separation from service to comply with
the specified employee rules of Section 409A it shall be so delayed
(but not more than is required to comply with such rules).  9.             Assignment.  Neither the Executive nor the Company may
make any assignment of this Agreement or any interest in it, by operation of
law or otherwise, without the prior written consent of the other; provided,
however, that the Company may assign its rights and obligations under this
Agreement without the Executives consent to one of its Affiliates or to any
Person with whom the Company shall hereafter affect a reorganization,
consolidate with, or merge into or to whom it transfers all or substantially
all of its properties or assets.  This
Agreement shall inure to the benefit of and be binding upon the Executive and
the Company, and each of our respective successors, executors, administrators,
heirs and permitted assigns.  10.           Severability.  If any portion or provision of this Agreement
shall to any extent be declared illegal or unenforceable by a court of
competent jurisdiction, then the remainder of this Agreement, or the
application of such portion or provision in circumstances other than those as
to which it is so declared illegal or unenforceable, shall not be affected
thereby, and each portion and provision of this Agreement shall be valid and
enforceable to the fullest extent permitted by law.  11.Miscellaneous.  This Agreement, together with the Stock
Restriction Agreement and the Confidentiality, Non-Competition and Proprietary
Information Agreement, sets forth the entire agreement between the Executive
and the Company and replaces all prior communications, agreements and
understandings, written or oral, with respect to the terms and conditions of the
Executives employment.  This Agreement
may not be modified or amended, and no breach shall be deemed to be waived,
unless agreed to in writing by the Executive and an expressly authorized
representative of the Board.  The
headings and captions in this Agreement are for convenience only and in no way
define or describe the scope or content of any provision of this Agreement.  This Agreement may be executed in two or more
counterparts, each of which shall be an original and all of which together
shall constitute one and the same instrument. This is a Massachusetts contract
and shall be governed and construed in accordance with the laws of the
Commonwealth of Massachusetts, without regard to the conflict-of-laws
principles thereof.  12.           Notices.  Any notices provided for in this Agreement
shall be in writing and shall be effective when delivered in person, consigned
to a reputable national courier service for overnight delivery or deposited in
the United States mail, postage prepaid, and addressed to the Executive at the
Executives last known address on the books of the Company or, in the case of  9


the Company, to it by
notice to the Chairman of the Board of Directors, c/o Sirtris Pharmaceuticals, Inc.
at its principal place of business, or to such other address(es) as either
party may specify by notice to the other actually received.  10


IN WITNESS
WHEREOF, this Agreement has been executed as a sealed instrument by the
Company, by its duly authorized representative, and by the Executive, as of the
date first above written.  THE EXECUTIVE
  
  THE COMPANY/s/ Christoph Westphal
  
  By:
  /s/ Garen BohlinChristoph WestphalTitle:
  Chief Operating Officer  11